Objective: Frequent demands from others in relationships are associated with worse physiological and health outcomes. The present research investigated 2 potential moderators of the relationship between frequency of demands from one’s family and inflammatory profiles among adolescents: (a) closeness of adolescents’ relationships with their families, and (b) the frequency with which adolescents provided help to their families. Method: Two hundred thirty-four adolescents, ages 13–16 (Mage = 14.53; 47.83% male), completed a daily dairy in which they reported on the frequency of demands made by family members. They were also interviewed about the closeness of their family relationships and reported in the daily diary on how frequently they provided help to their families. Adolescents also underwent a blood draw to assess low-grade inflammation and proinflammatory cytokine production in response to bacterial stimulation. Results: More frequent demands from family predicted higher levels of low-grade inflammation and cytokine production in response to bacterial stimulation in adolescents. Family closeness moderated the relationship between frequent demands and stimulated cytokine production such that more frequent demands predicted higher cytokine production among adolescents who were closer to their families. Furthermore, frequency of providing help moderated the relationship between frequent demands and both low-grade inflammation and stimulated cytokine production, such that more frequent demands predicted worse inflammatory profiles among adolescents who provided more help to their families. Conclusions: These findings build on previous work on family demands and health to show under what circumstances family demands might have a physiological cost.