Context frames such as describing a Prisoner’s Dilemma as a “community” or a “stock exchange” game cause significant variation in cooperative behaviour. Here, we draw on recent advances in research on situation construal to propose that perceived conflict of interests is a mechanism underlying framing effects on cooperation in experimental games. Specifically, we argue that people readily think about situations in terms of conflicts of interests, and how people perceive the conflict of interests in different games predicts differences in cooperation across these games. In a formal model, we show that variation in perceived conflict of interests can affect cooperative decisions even when first-order beliefs and social preferences are static. We test this model across two studies (total N = 1,615). In each study, we elicited situation perceptions and beliefs about others’ behaviour in a framed game. The basic framing effect replicated in a dichotomous-choice Prisoner’s Dilemma (study 1), but not in a continuous-choice Prisoner’s Dilemma (study 2). Perceptions of conflict of interests mediated between framing and cooperative behaviour, whereas beliefs and preferences did not. Exploratorily, perceptions of conflict of interests had a causal effect on cooperative behaviour when induced orthogonally to the frame. This study provides evidence for perceptions of conflict of interests as a mechanism underlying framing effects and integrates framing effects with the wider literature on situation perception. Moreover, it supports a causal role of situation perception in social decision-making. However, the results also call into question the generalisability of framing effects.