Abstract Purpose Social isolation has negative effects on physical and brain health across the lifespan. However, the prevalence of social isolation, specifically with regard to sociodemographic and socioeconomic factors, is not well known. Methods Database was the Leipzig population-based study of adults (LIFE-Adult Study, n = 10,000). The short form of the Lubben Social Network Scale (LSNS-6) was used to assess social isolation (cutoff < 12 points). Sampling weights were applied to account for differences in sampling fractions. Results Data were available for 9392 study participants; 51.6% were women, the mean age was 45.2 years (SD = 17.3). The prevalence of social isolation was 12.3% (95% CI 11.6–13.0) across ages 18–79 years. Social isolation was more prevalent in men (13.8%, 95% CI 12.8–14.8) compared to women (10.9%, 95% CI 10.0–11.8; $χ^{2}$ χ 2 (1) = 18.83, p < .001), and it showed an increase with increasing age from 5.4% (95% CI 4.7–6.0) in the youngest age group (18–39 years) to 21.7% (95% CI 19.5–24.0) in the oldest age group (70–79 years; $χ^{2}$ χ 2 (4) = 389.51, p < .001). Prevalence differed largely with regard to socioeconomic status (SES); showing lower prevalence in high SES (7.2%, 95% CI 6.0–8.4) and higher prevalence in low SES (18.6%, 95% CI 16.9–20.3; $χ^{2}$ χ 2 (2) = 115.78; p < .001). Conclusion More than one in ten individuals in the adult population reported social isolation, and prevalence varied strongly with regard to sociodemographic and socioeconomic factors. Social isolation was particularly frequent in disadvantaged socioeconomic groups. From a public health perspective, effective prevention of and intervention against social isolation should be a desired target as social isolation leads to poor health. Countermeasures should especially take into account the socioeconomic determinants of social isolation, applying a life-course perspective.