This study investigated the stress-buffering effect of social support on immune function and infectious risk in women with breast cancer, during and after chemotherapy. Data were collected from 50 women with breast cancer before and after their chemotherapy, as well as three months later. Stress was measured by daily hassles related to cancer and social support by marital status (MS) and perceived support from friends (Ps-fr). Blood was collected to measure innate immune markers (i.e., T cells, NK cells and neutrophils). Infections were evaluated using a semi-structured interview. Moderation, mediation and moderated mediation models were computed to test the hypotheses. Higher stress at baseline was found to significantly predict a higher occurrence of infections during chemotherapy, but not three months later. The relationship between stress and infections was not significantly explained by any of the immune markers. The interaction between stress and social support was tested using MS alone and combined with Ps-fr. A protective effect of social support on the deleterious effect of stress on infectious risk was found. Single patients reporting lower Ps-fr showed the strongest association between stress and infections, while the weakest association was found in patients in a committed relationship with a higher level of Ps-fr. Women experiencing more stress before the beginning of chemotherapy would appear to be at a higher risk of developing infections during their treatment. Results of this study also suggest that this effect could be buffered by the presence of a romantic partner and by higher Ps-fr. •The buffering effect of social support in the relationship between stress, immune function and infectious risk has yet to be explored in cancer.•Results of this study showed that a higher stress level prior to chemotherapy was associated with an increased risk for infections during chemotherapy.•The relationship between stress and infections was not significantly mediated by immune alterations.•The buffering effect of social support was supported: Single patients reporting lower support from their friends showed the strongest association between stress and infections.•The weakest association was found in patients in a committed relationship with a higher perceived support from friends.