The immune system allows animals to survive the constant attacks of pathogens. Even though it is essential for survival and fitness, the performance of the immune system can decline with age -a process known as immunosenescence- which may be responsible for the increased mortality of older individuals. There are few studies regarding the effect of age on the immune system in reptiles, and no evidence of immunosenescence has yet been reported in lizards. In a wild population of Dickerson's collared lizards, Crotaphytus dickersonae, we evaluated the effect of age (estimated by skeletochronology) on the male’s immune response to a novel antigen (phytohemagglutinin). We found a strong negative relationship between immune response and age, the first evidence of immunosenescence in a lizard. Our results show that immunosenescence can occur even in relatively short-lived reptiles and underline the importance of age on performance in fitness-related traits.