Animal and human studies show that exposure to solar-simulated UVR is immunomodulatory. Human studies that used natural sun exposure and controlled for confounding are rare. We immunized 217 healthy adults (age range = 18–40 years) with a T-cell–dependent antigen, keyhole limpet hemocyanin, and measured personal clothing-adjusted UVR exposure (for 5 days before and after immunization), lifetime cumulative UVR exposure, serum 25-hydroxyvitamin D concentration at immunization, and potential confounding factors. We tested cellular and humoral immune responses in relation to UVR exposure. The delayed-type hypersensitivity response to keyhole limpet hemocyanin recall challenge was lower in individuals with higher personal clothing-adjusted UVR exposure on the day before immunization (P = 0.015) and during intervals spanning the day before to 2–3 days after immunization. There was an incremental increase in T helper type 17 cells (as a proportion of CD4+ T cells) from preimmunization to postimmunization in the high, compared with the low, personal clothing-adjusted UVR exposure group (0.31% vs. –0.39%, P = 0.004). Keyhole limpet hemocyanin-specific antibody titers were not associated with acute or cumulative UVR exposure or serum 25-hydroxyvitamin D levels. Higher UVR exposure at antigen sensitization was associated with a reduced delayed-type hypersensitivity response and altered T helper type 17 kinetics. This has implications for the effectiveness of vaccinations and susceptibility to infections that rely on cell-mediated immune responses.