Background The importance of vitamin D (VD) in systemic lupus erythematosus (SLE) is being increasingly appreciated, with studies suggesting a relationship between VD deficiency and SLE onset/disease activity. We investigated VD status in SLE patients and its associations with disease activity in a geographical region of India receiving low solar ultraviolet-B (UV-B) index. Materials and methods We enrolled 109 SLE patients along with 109 healthy controls belonging to same ethnicity and localities. Demographic and clinico-laboratory information were recorded. VD status was assessed by estimating serum 25-hydroxyvitamin D (25-OH-D) concentrations (deficient: Results Hypovitaminosis D was prevalent in 90.83% SLE patients [vs. 77.98% healthy controls; chi-squared (χ2) = 10.125, df = 2, p < 0.01]. SLEDAI scores and 25-OH-D values were inversely associated, which extended in a two-way manner as revealed by multiple logistic regression models. SLE patients with VD deficiency were more likely to have high/very high disease activity [adjusted odds ratio (OR) = 3.5, 95% confidence intervals (CI): 1.4–8.9]. Conversely, patients with high SLEDAI scores (>10) also had greater risks of being VD deficient (adjusted OR = 3.9, 95% CI: 1.5–10.8). Conclusion VD deficiency is widespread in SLE. The relationship appears to be bidirectional, with VD status associated both as determinant and outcome of disease activity in SLE.