||Backgrounds & aims: Vitamin D insufficiency is associated with worse clinical outcomes in multiple cancer types; however, its roles in diffuse large B-cell lymphoma (DLBCL) patients are still unclear. Here, we aimed to determine the prognostic values of circulating total 25(OH)D and bioavailable 25(OH)D levels in DLBCL patients. Methods: A total of 332 newly diagnosed DLBCL patients were recruited. The plasma total 25(OH)D and bioavailable 25(OH)D levels at diagnosis were determined, and their associations with the clinical characteristics and the prognosis of patients were evaluated. The predictive values of clinical characteristics and 25(OH)D levels in the responses to R-CHOP treatments in DLBCL patients were also assessed. Results: Of the patients, 92.8% had insufficient vitamin D status (<30 ng/mL). Patients with higher plasma bioavailable 25(OH)D were associated with better progression-free survival (PFS, multivariate adjusted-HR = 0.72, 95% CI = 0.38-1.35, P = 0.301, Tertile 2 vs. 1; multivariate adjusted-HR = 0.39, 95% CI = 0.20-0.79, P = 0.009, Tertile 3 vs. 1) and overall survival (OS, multivariate adjusted-HR = 0.89, 95% CI = 0.39-2.02, P = 0.777, Tertile 2 vs. 1; multivariate adjusted-HR = 0.21, 95% CI = 0.07-0.65, P = 0.007, Tertile 3 vs. 1). Meanwhile, higher plasma total 25(OH)D level was significantly associated with better PFS but not OS in DLBCL patients. Besides, DLBCL patients with higher total or bioavailable 25(OH)D levels were more sensitive to the R-CHOP regimen treatments. Conclusion: The bioavailable 25(OH)D level may serve as a novel prognostic biomarker in DLBCL patients. (C) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.