Purpose: Lifestyle changes associated with end-stage renal disease may be a factor in depression and quality of life (QOL) for patients receiving hemodialysis. This cross-sectional study examined the relationship between nutritional status, QOL, and depression in 124 hemodialysis patients. Methods: Nutritional markers included serum albumin, normalized protein catabolic rate (nPCR), body mass index (BMI), body fat percentage, and daily protein intake. Physical and Mental dimension scores of the Kidney Disease QOL-Short Form (KDQOL-SF), and the Center for Epidemiological Studies of Depression (CESD) survey were used to measure QOL and depression, respectively. Data were analyzed using regression analyses. Measures of effect size were used for interpretation. Results: Nutritional status indicators explained a moderate amount of the variability of the Physical dimension of QOL (crude R2 =.14, covariate-adjusted ΔR2 =.06) but had weak explanatory ability for the Mental dimension of QOL (crude R2 =.05, covariate-adjusted ΔR2 =.02) and CESD (crude R2 =.02, covariate-adjusted ΔR2 =.005). Additional findings suggested the presence of non-linear relationships between protein intake and both the Physical and Mental QOL dimension scores. Longer dialysis vintage was also correlated with lower psychosocial patient outcomes. Conclusion: While nutritional status is an important element in predicting hemodialysis patient outcomes, its relationship to depression and QOL, in this sample, demonstrated only moderate explanatory ability. However, dialysis vintage and level of education had a significant relationship with depression and QOL. These findings suggest that patients with longer dialysis vintage and limited health literacy require unique plans of care. Future studies aimed at understanding the interrelationships between non-modifiable patient characteristics and psychosocial outcomes are imperative.