Changes to one’s pain processing system through external or cognitive influences may influence how we interact with other people. To investigate the causal effects of different pain modulations on social emotions and behaviour, we conducted a pre-registered PRISMA-guided systematic literature review. Our main aim was to investigate how directly or indirectly interfering with pain perception through (psycho)pharmacological manipulations affects our abilities to perceive, process, and react to positive and negative emotions (including pain) in other individuals. We included and synthesized 50 of 2060 screened studies. Included studies investigated the effects of opioids, opioid antagonists, acetaminophen, capsaicin, cannabinoids, ketamine, alcohol, placebo analgesia, and hypnotic analgesia. Overall risk of bias was low in 23, medium in 12, and high in 14 studies, while only 24% of studies checked whether their employed manipulation reduced first-hand pain (which it did in all of these). In summary, studies report inconsistent results, with findings generally showing small effects in both directions, ie, an increase or decrease of social emotions or abilities. The strongest and most consistent effect was observed for placebo analgesia decreasing empathy for pain. These results can be attributed to study heterogeneity, pharmacological effects, modes of action, as well as dosage differences. This review thus shows that we are far away from understanding the intricacies of different (psycho)pharmacological pain manipulations and their effects on social emotions and behaviour. To advance as a field and better understand the mechanisms of this interplay, we need well-powered studies, large-scale replications, and systematic meta-analyses.