To determine the incidence of depression in head and neck cancer (HNCA) patients following definitive treatment and the relationship between depression and head and neck-specific measures of quality of life and function. Prospective cohort analysis. Two hundred forty-six patients were evaluated with the Beck Depression Inventory Fast-Screen (BDI-FS), University of Washington Quality of Life (UW QOL), Voice Handicap Index (VHI), and MD Anderson Dysphagia Inventory (MDADI) questionnaires. Patients with a preexisting diagnosis of depression were excluded. Complete 1-year post-treatment data were available for 46 HNCA patients, with depression identified in nine patients (20%). On multivariate analysis, depression was significantly associated with poorer global UW QOL (β = -40.3, P < .001) and overall MDADI scores (β = -21.8, P = .038), but not with VHI scores, after controlling for other clinical variables including initial treatment modality. BDI-FS scores were significantly correlated with global UW QOL (r = -0.7, P < .001) and overall MDADI scores (r = -0.5, P = .0045), and global UW QOL correlated significantly with overall MDADI scores (r = 0.4, P = .0166). After controlling for clinical variables, MDADI, and VHI scores, only depression was associated with global UW QOL score (β = -30.5, P = .019). There is a high incidence of depressive symptoms in HNCA patients at 1 year following definitive therapy, which is independent of primary treatment modality and is associated with poorer global QOL and MDADI scores. Although depression and swallowing function are highly correlated, depression has a greater effect on QOL than swallowing scores, suggesting that early identification and aggressive treatment of patients with depressive symptoms is warranted to maximize post-treatment QOL.