Introduction Patients with systemic lupus erythematosus (SLE) frequently present low levels of vitamin D. However, studies that have evaluated its association with disease activity have generated contradictory results. Methods A cross-sectional study was carried out on patients diagnosed with SLE in two hospitals in Manizales, Colombia. Disease activity was evaluated by the SLE disease activity index 2000 (SLEDAI-2K) and serum concentration of 25-hydroxyvitamin D (25(OH)D) was measured by chemiluminescence. The correlation analysis was accomplished with the Spearman correlation coefficient. Results The study included 51 patients. The median SLEDAI-2K score was 8 points. The mean serum level of 25(OH)D was 24.5 ng/ml. Of the participants, 37.3% had vitamin D insufficiency and 35.3% had deficiency. An inverse correlation was found between the levels of the 25(OH)D and the SLEDAI-2K score ( r = –0.578, p < 0.001), being greater in late-onset lupus, with absence of polyautoimmunity and in patients using glucocorticoids. Conclusions Low levels of vitamin D are frequent in SLE, presenting an inverse correlation with the disease activity. This is influenced by the use of glucocorticoids, the presence of late-onset lupus and the absence of polyautoimmunity.