To examine the hypothesis that the association between vitamin D deficiency and depressive symptoms is dependent upon total cholesterol level in a representative national sample of the South Korean population.

This was a population-based cross-sectional study.

The Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010–2012).

We included 7198 adults aged 20–88 years.

The incidence of depressive symptoms in individuals with vitamin D deficiency (serum 25-hydroxyvitamin D<20 ng/ml) was 1·54-fold (95 % CI 1·20, 1·98) greater than in individuals without vitamin D deficiency (serum 25-hydroxyvitamin D ≥20 ng/ml). The relationship was stronger in individuals with normal-to-borderline serum total cholesterol (serum total cholesterol<240 mg/dl; OR=1·60; 95 % CI 1·23, 2·08) and non-significant in individuals with high serum total cholesterol (OR=0·97; 95 % CI 0·52, 1·81) after adjustment for confounding variables (age, sex, BMI, alcohol consumption, smoking status, regular exercise, income level, education level, marital status, changes in body weight, perceived body shape, season of examination date and cholesterol profiles).

The association between vitamin D deficiency and depressive symptoms was weakened by high serum total cholesterol status. These findings suggest that both vitamin D and total cholesterol are important targets for the prevention and treatment of depression.