Actual and perceived social isolation are both associated with increased risk for early mortality. In this meta-analytic review, our objective is to establish the overall and relative magnitude of social isolation and loneliness and to examine possible moderators. We conducted a literature search of studies (January 1980 to February 2014) using MEDLINE, CINAHL, PsycINFO, Social Work Abstracts, and Google Scholar. The included studies provided quantitative data on mortality as affected by loneliness, social isolation, or living alone. Across studies in which several possible confounds were statistically controlled for, the weighted average effect sizes were as follows: social isolation odds ratio (OR) = 1.29, loneliness OR = 1.26, and living alone OR = 1.32, corresponding to an average of 29%, 26%, and 32% increased likelihood of mortality, respectively. We found no differences between measures of objective and subjective social isolation. Results remain consistent across gender, length of follow-up, and world region, but initial health status has an influence on the findings. Results also differ across participant age, with social deficits being more predictive of death in samples with an average age younger than 65 years. Overall, the influence of both objective and subjective social isolation on risk for mortality is comparable with well-established risk factors for mortality.