In Minneapolis, a man in town for a convention goes jogging at night. A somewhat overweight man jogs past him and then stops further down the path. When the conventioneer stops to congratulate the second jogger on being faster, the second jogger thrust his hand into the conventioneer's chest and rip his heart out.
As Sam and Dean wander a farmer's market, Dean goes over the news and finds a report about the Minneapolis murder. There is also a news story on a similar murder in Minneapolis six months ago. Dean is eager to investigate but Sam points out that they've already got enough going on looking for Kevin and the tablet. As Sam shops at the stalls, buying fresh fruit, Dean reminds him yet again that Sam quit for a year and asks if they should shop for produce while people are getting killed.
Sam gives in and the Winchesters drive to Minneapolis. Posing as FBI agents, they talk to Detective Pike, who resents their questions about how he handled the case. They found no leads but have surveillance video of the jogging path. It shows the jogger passing the murder victim and Pike informs them that they identified the man as Paul Hayes, a local. Paul said that he didn't see anything after passing the victim and that he has a clean criminal record, so the police had no choice but to let him go.
The Winchesters go to visit Paul, who tells them that he didn't know the conventioneer and that he didn't see anything after passing him on the path. Sam points out that Paul is a bit overweight and the man admits that he had a health scare a year ago and has been exercising ever since. When Paul tells them nothing useful, Sam and Dean go to a bar to compare notes. Dean searched Paul's apartment but didn't find any supernatural items or spell books. When he checks the Internet, Dean discovers that there was another murder in Ames, IA, on the night that the police were questioning Paul. There was also a similar murder six months ago in Ames but this time the police captured the killer: a fellow officer, Arthur Swenson.
The brothers go to the Ames police station and talk to Captain Levitt, who admits that Swenson was a perfect officer. However, they found the dead man in front of Swenson's house and Swenson covered in blood and sobbing on the steps. The Winchesters confirm that Swenson was in court testifying during the preceding few days when the murder in Minneapolis occurred. They go to see Swenson, who is muttering something repeatedly in a foreign language and refuses to acknowledge them. They test him with holy water but there's no sign that he's demon possessed.
That night, Swenson is in his cell and wrenches out a bunk strut with superhuman strength. He then drives the jagged edge into his right eye.
At their motel, Dean tries a translation app on Sam's recording of Swenson but it can't provide a translation. The police call them about Swenson blinding himself and Dean goes to see him at the hospital. The attending physician, Dr. Kashi, explains that Swenson deliberately cut out his left eye. Dean remembers that Swenson had different colored eyes when he saw him earlier and Kashi confirms that Swenson lost his left eye in an accident one year ago and received a donor organ. He sweet talks her into calling him when she can determine the donor and leaves.
When Dean goes back to the motel, Sam tells him that he checked Paul's medical records and found out that he also had a transplant one year ago. He also tells Dean that emailed a copy of the recording to Dr. Morrison, who helped them before. While they wait for Dean to get back to them, Dean says that they need to go to Boulder, CO, because the next murder in the series occurred there.
In Boulder, a sleazy guy, Chick, waits outside a strip for one of the strippers, Randa Monroe, to come out. When she does, he tries to make small talk with her and Ronda leads him down an alley... and then rips his heart out.
As they drive to Boulder, Dean is enthused about how the case is going and that the two of them are together again, hunting monsters. Sam suggests that Dean doesn't need him and that he wants his time to count. Kashi calls Dean to tell him that Paul received a pair of kidneys from the same donor as Swenson: famous quarterback Brick Holmes. Brick lives in Colorado and died in a car accident, and eight of his organs were donated to needy patients.
Randa goes to a chamber at a house and performs a ritual. She paints herself with the blood from Chick's heart and then eats it, and a burst of energy fills her body.
Sam and Dean arrive in Boulder and meet with Eleanor Holmes, Brick's mother. She explains that her son sought physical perfection and that he signed up as an organ donor as part of a publicity event. Dean tries to find out if there was anything mysterious about Brick's accident and if he was involved with the occult, and Eleanor abruptly tells them that she has an anniversary ceremony for her son's death and they'll have to leave. As they go, Dean spots another report about a similar murder. In the house, Eleanor watches the brothers go and Randa comes down. She wonders who Sam and Dean were and warns Eleanor to do say anything that could give them away. When Eleanor says that she won't, Randa reminds the older woman that she has Brick's heart, giving her new life, and she came to Boulder to be with her... and because Brick needs both of them.
The brothers check in at a motel and Morrison contacts Sam with a translation. Swenson was speaking in ancient Mayan, saying, "The divine god Cacao is born." Cacao is the Mayan god of corn and the most powerful of the Mayan deities. Meanwhile, Dean confirms that the next donor, Jimmy Yang, lives in Phoenix and has disappeared. He tells Sam that he also saw an email to him about his application to college. Sam insists that he's just considering his options and Dean drops the matter for the moment so that they can focus on Eleanor.
The Winchesters break into Eleanor's house and search the place. Sam finds Eleanor's dress in Brick's closet and they wonder if she was sleeping with her son. Dean finds a hidden room filled with sports memorabilia. However, there are dozens of trophies besides football. They also find a box of letters all written from Brick to someone named Betsy. The earliest ones date back to the 1940s and in each one, Brick talks about competing in a different sport and winning. In the last one, Brick says that he's tired of it all.
Back at the hotel, Sam checks the Internet and confirms that all of the people that won the trophies mentioned in the letters all look much the same, and they all like Brick. Based on the letter dates, Brick is at least 95 years old and remained in peak physical condition. Dean figures that since in Mayan cultures, athletes were treated as gods and ate human hearts to gain superhuman strength, Brick may be a Mayan and over 900 years old. They figure that Brick made a deal with Cacao to keep himself young as well as virile. When the donor recipients received Brick's organs, they all became part of the deal and were able to kill people and gain physical prowess. The older Swenson was the only one who snapped because of the guilt. Sam continues checking and finds a photo of one of Brick decades ago with Betsy... who is Eleanor.
The Winchesters go back to see Eleanor and tell her that they know the truth. She insists that she didn't know about the murders and thought that the sacrifices would end once Brick Died. Dean asks for her help and Eleanor tells the Winchesters that Brick was actually Inyo, a Mayan athlete born 1,100 years ago. He didn't want to lose his athleticism so he made a deal with Cacao, offering the god two hearts a year at the beginning of planting and harvesting season. When they met in the 1940s, they fell in love and Eleanor ignored what Brick was doing so that she could be with him. Every ten years or so they assumed new identifies when people would start realizing that Brick wasn't aging. When Eleanor reached her 40s, she posed as Brick's mother instead of his girlfriend. When he realized that she would die, Brick couldn't bear it and killed himself in the car accident. Dean tells her that they now have to deal with eight killers but Eleanor tells them that if they can destroy Brick's still-beating heart then it will end the curse for all of them... and she knows who has the heart.
The brothers go to Randa's strip club during the day when it's closed and the brothers go in to find her and remove Brick's heart. Randa comes out on stage and, realizing that Eleanor betrayed her, warns the Winchesters that it won't go well for them or Eleanor. As the brothers come after her, the other donor recipients, including Paul and Jimmy Yang, attacks the brothers. They knock Sam out and pin Dean down on the stage, and Randa tells Dean that she was a weak little Georgia girl. When her heart gave out, she received Brick's and now she's a warrior and doesn't want to lose the sensation, which is better than sex. She rips open Dean's shirt and starts to rip in, but Sam revives and knocks the men off. Dean grabs his knife and stabs Randa, and the heart is consumed in a burst of energy. The organs in the other men explode as well as Randa collapses, dead.
Later, the Winchesters return to tell Eleanor that it's finally over and she's glad to be at peace. As the brothers drive off, Dean asks Sam if it felt good to fight monsters again. Sam says that he doesn't feel like a table and is quitting once they find Kevin and the tablet. Dean doesn't believe it, but Sam says that he had a year to experience a normal life and that's all that he wants. As they drive away, Sam remembers celebrating a birthday with Amelia and their dog, Riot.