Introduction and objectives: Although loneliness and social isolation are growing public health concerns, there is little knowledge of the experience of medical residents who are usually young adults. We aimed to explore the prevalence and associated risk factors of loneliness and social isolation in medical residents.Method: A multi-center cross-sectional study that included 1,338 medical residents from eight centers in China was conducted in February 2020. A self-report questionnaire was used to record participants’ demographic characteristics, dietary habits, life-related factors, work-related factors, and psychological outcomes. Loneliness and isolation were measured using the Revised UCLA loneliness scale. Multiple logistic analysis was used to determine the adjusted odds ratio (OR) with 95% confidence intervals.Results: The effective response rate was 87.28% (1,338/1,533). Of the respondents, 24.40% reported loneliness and 44.50% reported social isolation. Three shared independent factors for loneliness and social isolation were identified: sleep quality (OR = 1.189; OR = 1.197; P < 0.001 for both), marital status (married vs. single, OR = 0.565, P = 0.007; OR = 0.486, P = 0.022) and perceived organization support (OR = 0.966; OR = 0.970, P < 0.001 for both).Conclusions: There is considerable prevalence of loneliness and social isolation among medical residents in China. Poor sleep quality, singlehood, and the absence of organizational support are shared risk factors for both loneliness and social isolation. Policymakers are encouraged to develop comprehensive strategies for preventing loneliness and social isolation.