This study examined the link between serum 25-hydroxyvitamin D (25(OH)D) and mortality in patients with colon cancer. Using a clinical database from the University of California, serum 25(OH)D measures were averaged for the time following diagnosis until either the time of death or 5 years had elapsed. Analytical methods included the use of Generalized Additive Models (GAM), logistic regression, and Cox proportional hazards models to examine non-linear relationships and the impact of 25(OH)D on 5-year mortality. This study assessed 1,602 patients with colon cancer having a median 25(OH)D of 31.8 ng/mL and a 5-year mortality rate of 22.7%. A significant association between higher post-diagnosis vitamin D levels and decreased 5-year mortality was observed. This association persisted after adjusting for disease severity and significant demographic confounders, in both a logistic regression model for 5-year mortality (OR = 0.79, 95% CI: 0.66-0.92, p < 0.001) and a cox proportional hazards model for survival (HR = 0.94, CI: 0.88-0.99, p = 0.048). GAM illustrated a steep increase in survival probability up to a plateau, suggesting a threshold effect beyond roughly 50.0 ng/mL. This study found a potential protective role of vitamin D in the survival of colon cancer patients, supporting the correction of levels below 25 ng/mL but ideally above 50 ng/mL.