Purpose: The interrelated associations of social relationship factors, depression, and outcomes of surgical patients are yet unexplored. The purpose of this study was to investigate whether depression mediates effects of general social support, loneliness, and living alone on hospital length of stay (LOS) of 2487 patients from diverse surgical fields.Method: Social relationship factors and depression were assessed prior to surgery. The PROCESS macro for SPSS was used to conduct three simple mediation models that tested the indirect effects of social relationship factors on LOS mediated through depression. The models were adjusted for age, gender, preoperative physical health, surgical field, severity of medical comorbidity, and extent of surgical procedure.Results: Social support and loneliness had significant indirect effects on LOS that were statistically mediated by preoperative depression. Lower social support and the feeling of loneliness were considerably related to higher depression which predicted longer LOS. While social support and loneliness had no direct effects on LOS, there was a small significant direct association of living alone with shorter LOS.Conclusion: Data suggest that social support and loneliness are indirectly related with surgical outcomes by an association with depression which in turn is related to worse outcomes.Trial Registration: NCT01357694 [ABSTRACT FROM AUTHOR]