BACKGROUND & AIMS: Low serum 25-hydroxyvitamin D (25OHD) is common in obese people. Obesity is associated with a state of low-grade inflammation (meta-inflammation). There is an increasing evidence indicating that vitamin D has anti-adipogenic activity and immunoregulatory effect. This study aimed to assess the effect of vitamin D supplementation on meta-inflammation and fat mass in obese subjects with vitamin D deficiency. MATERIALS AND METHODS: In this double-blind placebo-controlled randomized clinical trial, 44 obese subjects with vitamin D deficiency (25OHD < 50 nmol/L) were assigned into vitamin D (a weight reduction diet + bolus weekly dose of 50 000 IU vitamin D) or placebo group (weight reduction diet + edible paraffin weekly) for 12 weeks. Weight, fat mass and serum levels of 25OHD, calcium, parathyroid hormone (PTH), monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL-1β) and Toll-like receptor 4 (TLR4) were assessed before and after the intervention. RESULTS: Vitamin D supplementation resulted in significant increase of serum 25OHD level (P < 0.001), and significant decrease in PTH (P < 0.001), MCP-1 (P < 0.05), IL-1β (P < 0.05) and TLR-4 (P < 0.05); compared to the baseline values in vitamin D group. Weight, BMI and fat mass decreased in both groups (P < 0.05). Between the groups, there were significant decrease in weight, fat mass, serum MCP-1 and PTH concentrations and significant increase in serum 25OHD concentrations after intervention with vitamin D supplementation compared to placebo (P < 0.05). CONCLUSIONS: Improvement in vitamin D status in obese subjects with vitamin D deficiency in combination with weight loss diet resulted in weight, fat mass and MCP-1 decrease. Weight loss and vitamin D supplementation may act synergistically to reduce levels of meta-inflammation.