In social interactions, people frequently encounter gain (i.e., all outcomes aregains from the status-quo) or loss (all outcomes are losses from the status-quo)social dilemmas, where their personal interests conflict with social interests.We ask whether there are any behavioral differences in social interactions whenit comes to gains and losses. Using the Prisoner’s Dilemma games, inthree studies we observed that participants were less cooperative in the lossdomain than in the gain domain. This effect was robust, not moderated by payoffamount (Study 1), cooperation index (Study 1), domain comparison (Studies 1 and2), and personal loss aversion (Study 3). Social motive and belief explainedthis effect: compared to the gain domain, participants in the loss domainaroused more pro-self motive and less prosocial motive, and showed strongerbeliefs that their partner would defect, which led them to cooperate less. Thesefindings suggest that gain and loss domains affect individual motivation andbelief, subsequently affecting strategic choices in social dilemmas.