This study aimed to evaluate the effects of vitamin D3 and omega-3 fatty acids cosupplementation on inflammation and nutritional status in colorectal cancer patients. In this clinical trial, 81 colorectal cancer patients were randomly assigned into four groups: (1) control group: receiving a vitamin D3 placebo weekly + omega-3 fatty acid placebo capsules daily; (2) omega-3 fatty acid group: receiving 2 omega-3 fatty acid capsules (each capsule containing 330 mg of omega-3 fatty acids) daily + a vitamin D3 placebo weekly; (3) vitamin D group: receiving a 50,000 IU vitamin D3 soft gel weekly + 2 omega-3 fatty acid placebo capsules daily; (4) cosupplementation group: receiving a 50,000 IU vitamin D3 soft gel weekly + 2 omega-3 fatty acids capsules daily for 8 weeks. Before and after the intervention, height, weight, fat-free mass (FFM), serum levels of 25(OH)D, tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6), C-reactive protein (CRP), and albumin, were measured. After 8 weeks of intervention, patients who received combined vitamin D3 and omega-3 fatty acids supplements compared with omega-3, vitamin D3, and placebo groups had significantly decreased CRP and TNF-α. In addition, serum level of IL-6 was decreased significantly in omega-3, vitamin D3, and cosupplementation groups compared with baseline. Regarding nutritional status, weight, BMI, and FFM% were increased significantly in vitamin D3, omega-3, and cosupplementation groups at the end of the intervention. Vitamin D3 plus omega-3 fatty acids cosupplementation in colorectal cancer patients has beneficial impacts on inflammation and nutritional status.