Purpose: Poor nutritional status is common and associated with mortality and morbidity in patients with head and neck cancer (HNC). While there are several established clinical risk factors for poor nutritional status during HNC radiotherapy, the complete aetiology is not known. The association of malnutrition with psychological factors has been recognised in other chronic illnesses but has not been studied in HNC patients who have higher levels of malnutrition and psychological disorder than many other patient populations. Method: Patients with HNC were assessed at three time points: week 1 of radiotherapy treatment (T1, n = 72), end of radiotherapy treatment (T2, n = 64) and 4 weeks post-radiotherapy treatment (T3, n = 58). Nutritional outcome was measured using the Patient-Generated Subjective Global Assessment, and psychological factors measured were depression, anxiety and adjustment style. Results: Linear mixed models indicated that a model containing the variables time, tumour site and baseline depression best explained malnutrition at T2 and T3 (−2 restricted log likelihood = 695.42). The clinical risk factors: cancer stage, number of radiotherapy fractionations, a PEG feeding tube, availability of a care giver and dietitian's informal clinical assessment did not predict later nutritional status. Conclusions: Depression is a modifiable risk factor for malnutrition among HNC patients undergoing radiation therapy, offering the potential to ameliorate malnutrition in this group. While the nature of any causal relationship between depression and malnutrition in HNC is yet to be understood, the utility of a short depression screen in predicting malnutrition has been demonstrated and could be adopted in clinical practice.