Poor sleep and low social support have each been associated with mortality and morbidity from chronic illness, and a small body of research suggests that the two interact to influence systemic inflammation whereby good social relationships may buffer the relationship between poor sleep and increased inflammation. The current study investigated interactions between sleep and social support in the prediction of inflammation in a clinical population (prehypertensive and hypertensive individuals) at high risk for the development of cardiovascular disease. Using a standardized subjective measure of sleep quality, we found that social support moderated the association between sleep and circulating levels of both IL‐6 and CRP, such that poor sleep appeared to confer a risk of increased inflammation only in those participants who also reported low social support. In women, the same relationship was observed for TNF‐α. These results extend previous findings into a clinical population and also demonstrate that sleep quality and social support interact in the prediction of two previously uninvestigated clinically relevant inflammatory markers (CRP and TNF‐α). High levels of perceived social support may compensate for the negative health impact of poor sleep quality and vice versa.