Background: Although previous findings with small samples indicated that sugar-sweetened beverages (SSB) consumption was associated with depressive symptoms in adolescents, the mediating effect of physical subhealth in the association is unknown. Methods: A survey was conducted among freshmen from 11 provinces in China. A food frequency questionnaire was used to collect dietary behavior, and patient health questionnaire-9 items was used to assess depressive symptoms. A generalized linear model was used to analyze the association between SSB consumption, physical sub-health and depressive symptoms. The structural equation model was used to analyze the mediating effect of physical sub-health. Results: Of the 31,856 participants, 36.5 % had positive depressive symptoms. After adjusting for variables, carbonate beverages (8 = 0.11; 95%CI: 0.07-0.15; P = 0.000) and milk tea (8 = 0.07; 95%CI: 0.01-0.13; P = 0.021) consumption was associated with depressive symptoms in boys. Carbonate beverages (8 = 0.09; 95%CI: 0.05-0.13; P = 0.000), tea beverages (8 = 0.09; 95%CI: 0.04-0.13; P = 0.000), and milk tea (8 = 0.08; 95%CI: 0.04-0.11; P = 0.000) consumption was associated with depressive symptoms in girls. The mediating effect of physical sub-health accounted for 81.3 % of the total effect in the mediating model of SSB associated with depressive symptoms. Limitations: Retrospective survey has certain information bias. Association observed in the cross-sectional study is uncertain. Conclusions: The present study suggests that the consumption of SSB associated with depressive symptoms in Chinese college students, and physical sub-health plays a complete mediating role in the association.