Current theories suggest that physical pain and social rejection share common neural mechanisms, largely by virtue of overlapping functional magnetic resonance imaging (fMRI) activity. Here we challenge this notion by identifying distinct multivariate fMRI patterns unique to pain and rejection. Sixty participants experience painful heat and warmth and view photos of ex-partners and friends on separate trials. FMRI pattern classifiers discriminate pain and rejection from their respective control conditions in out-of-sample individuals with 92% and 80% accuracy. The rejection classifier performs at chance on pain, and vice versa. Pain- and rejection-related representations are uncorrelated within regions thought to encode pain affect (for example, dorsal anterior cingulate) and show distinct functional connectivity with other regions in a separate resting-state data set (N = 91). These findings demonstrate that separate representations underlie pain and rejection despite common fMRI activity at the gross anatomical level. Rather than co-opting pain circuitry, rejection involves distinct affective representations in humans.