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Social isolation and poor sleep quality are independent predictors of poor health outcomes and increased biological risk for disease. We previously found in a small sample of older women that the presence of social ties compensated for poor sleep in associations with the inflammatory protein interleukin 6 (IL‐6). The current study extended those findings to a national sample of middle‐aged and older men and women. Using both subjective and objective sleep assessments, we found that in men, but not in women, social engagement moderated the association of subjective sleep complaints with both IL‐6 and the soluble adhesion molecule E‐selectin. Social engagement also moderated the link between sleep efficiency—assessed by actigraphy—and IL‐6 levels in men, but not in women. These results extend our previous work and bolster the suggestion that positive psychological functioning may compensate for …