We examined sex differences in preferences for sexual variety and novelty to determine whether the Coolidge effect plays a role in human sexuality. In two experimental studies that employed different manipulations, we found converging evidence that men showed a greater preference for variety in potential short-term mates than did women. In the first study, men (n = 281) were more likely than women (n = 353) to select a variety of mates when given the opportunity to distribute chances to have sex with different individuals in hypothetical situations. This sex difference was evident regardless of the targets’ attractiveness and age. Further, men found it more appealing if their committed romantic/sexual partners frequently changed their physical appearance, while women reported that they modified their physical appearance more frequently than did men, potentially appealing to male desires for novelty. In the second study, when participants were given a hypothetical dating task using photographs of potential short-term mates, men (n = 40) were more likely than women (n = 56) to select a novel person to date. Collectively, these findings lend support to the idea that sex differences in preferences for sexual variety and novelty are a salient sex-specific evolved component of the repertoire of human mating strategies.