Mucositis and muscle wasting are two common toxicity effects of cancer treatment in head and neck cancer (HNC). There is limited data evaluating cancer treatment toxicities in relation to vitamin status. This study aimed to assess changes in vitamin status during HNC treatment in relation to body composition, inflammation and mucositis. In this prospective cohort study, dietary intakes (3-day food record), plasma levels of vitamins and C-reactive protein (CRP) were assessed at baseline (at diagnosis) and post-treatment (after 6–8 weeks of radiation therapy with or without chemotherapy). Computed tomography images were used to quantify body composition. Mucositis information was collected from health records of patients. Twenty-eight HNC patients (age 60 ± 10 years) completed both study time points. Patients who developed mucositis had significantly lower dietary intake of vitamins and plasma 25-hydroxy vitamin D (25-OHD) and all-trans retinol levels (p < 0.02). Patients lost a considerable amount of muscle mass (3.4 kg) and fat mass (3.6 kg) over the course of treatment. There was a trend toward greater muscle loss in patients with 25-OHD < 50 nmol/L compared to patients with 25-OHD ≥ 50 nmol/L (p = 0.07). A significant negative correlation was found between plasma all-trans retinol and CRP level at the end of treatment (p = 0.03). Poor vitamin status could be a contributing factor in developing treatment-induced toxicities.