Sam Merlotte remains a major character in Season 4.
A year later Sookie returns to Bon Temps and Sam is frustrated with her for not telling anyone where she went. He tells her that a lot has changed while she's been gone.
A year after shooting his younger brother, Tommy Mickens, in the leg; Sam had found solace by finding a small group of shapeshifters to have group therapy sessions with. These fellow shapeshifters are animal activist Suzanne McKittrick, politically minded Emory Broome and teacher Luna Garza. After discussing issues in their private lives and providing support for one another over drinks and refreshments, the four shapeshifters strip off and transform themselves to horses, taking off into the night. ("She's Not There")
That same night, Sam begins flirting with Luna who seems to be interested in him too. He convinces her to open up to him and leans in for a kiss. After hesitating, Luna takes off and transforms back into a horse. The next day, Luna shows up at Sam's office and apologizes for last night. She tells Sam that she really wants to open up to him and the two kiss. Sam later escorts Luna out of his office and the two kiss again in public while Tommy jealously looks on.
While enjoying shifting with Luna, Sam notices that another shifter is nearby. He realizes it is Tommy, and chases after him. He catches him and confronts him about faking his leg. ("You Smell Like Dinner")
Tommy approaches Sam about how they could make money off of Maxine Fortenberry's land. Sam tells him to get lost and that Tommy better tell Maxine about the natural gas she has on her property. ("If You Love Me, Why Am I Dyin'?")
Sam spontaneously stops by Luna's home. There he is surprised to meet Emma, Luna's young daughter. He stays and enjoys the day and evening with them. Luna explains that her ex is a werewolf who is very jealous and could possibly be stalking her. ("I'm Alive and on Fire")
Sam takes Tommy to a hospital after discovering him unconscious with a high fever in a pool of bloody vomit. The doctor diagnoses him with food poisoning. Tommy lies to Sam and tells him that he must have eaten something that had poisoned him while running in a shifted form at the full moon. He mentions nothing of Luna's visit or his new skinwalking ability.
Sam goes to visit Luna at her school, after calling her and getting a cold response. She is still upset about his ill-treatment of her after they had sex the previous night. He explains that he had been dealing with the aftermath of a fire the previous night and could not have slept with her. He and Luna realize Tommy has skin-walked, which accounted for his high fever and vomiting. ("Cold Grey Light of Dawn")
Sam tries to convince Luna to forgive him. His brother Tommy used his skinwalker ability to pose as Sam and sleep with Luna. Sam tells her that he has disowned Tommy. He tells her that he can forgive Tommy for killing their parents but not for what he did to Luna. ("Spellbound")
Marcus is frustrated by Sam's relationship with Luna and protective of his daughter Emma. Marcus shows up at Luna’s house to tuck his daughter in. He is angry when he finds Sam there. Marcus tells Sam that he pissed on the wrong boots and leaves. ("Spellbound")
Luna urges Sam to leave her house because Marcus is not his problem. She tells him it will be worse for everyone if Marcus comes back and Sam is still there. Sam suggests a camping trip to help Emma forget the nights events. ("Let's Get Out of Here")
Luna and Sam are camping while Emma is chasing bunnies. Emma says that she longs to grow up and be a shifter. Sam hides and shifts into a bunny, delighting Emma. ("Let's Get Out of Here")
Tommy is badly beaten by Marcus' pack. Alcide brings Tommy back to Merlotte's, believing that he is near death. Sam wants to get him some V, but Alcide said that he has a right to choose his time. Tommy is laying on the pool table. He says he wants to disappear like he never was. As he’s dying, he tells Sam not to forget about him right away and that he was sorry for everything. Tommy dies and Sam plans to kill Marcus. ("Burning Down the House")
Sam goes to Marcus' shop and confronts Nate, one of the guys who helped kill his brother. He pulls a gun on him then begins to beat him up; Alcide intervenes and holds Sam back. ("Burning Down the House")
Alcide and Sam are at Marcus Bozeman's bike shop looking for Marcus, who caused Tommy to be murdered at the hands of his pack. Luna turns up at the bike shop saying that Marcus has taken Emma. Emma eventually calls Luna and tells her that she is at Alcide's house; Debbie and Marcus have slept together. ("Soul of Fire")
Alcide, Sam, and Luna find Emma in the living room. Sam gets Luna to take Emma out of the house so that he and Alcide can take care of Marcus. Alcide bursts into the bedroom where he finds the half-dressed Debbie with Marcus. Sam walks in, carrying a gun, but decides that he should fight Marcus as a man and not with weapons or in a shifted form. Sam beats Marcus to within an inch of his life but lets him go after seriously berating him. Marcus retaliates and picks up Sam's gun. Alcide manages to tackle Marcus to the ground before he has time to shoot anyone. Alcide then kills Marcus with one blow to the neck, breaking his neck and crushing his windpipe. Debbie starts screaming, then calms herself enough to say, "Everything will be alright" but Alcide abjures her. ("Soul of Fire")
Sam attends Tommy's funeral with Maxine Fortenberry and she tells him that, "While Tommy wasn't my flesh and blood, he was a son to me and Sam you should call me 'Momma' from now on." At Merlotte's, everyone is celebrating Halloween. Sookie comes in and talks to Sam who realizes that Tommy, while in Sam's form, had fired Sookie but he chooses not to tell her and gives her her job back. ("And When I Die")