Objective: To analyse sex differences in health-related quality of life (HRQL) before, during and up to 3 months posttreatment of head and neck cancer, and to examine the importance of salivary secretion rate for HRQL posttreatment. Methods: Patients were recruited before starting curative oncologic treatment. Clinical examinations were performed including determination of the stimulated salivary secretion rate. HRQL (EORTC C30 and HN35) was reported at baseline, weeks 2, 4 and 6 during treatment and 3 months after treatment. Results: A total of 56 men and 19 women were included. During treatment, men reported more problems with pain and sexuality, a higher use of painkillers and need for nutritional support during oncologic treatment, while women reported more problems with weight loss and dry mouth. At 3 months posttreatment, women reported more problems and symptoms than men with the highest scores noted for dry mouth, weight loss and sticky saliva. Patients with hyposalivation (<= 0.7 mL/min) posttreatment reported more problems and symptoms compared with those with a secretion rate of > 0.7 mL/min, especially regarding dry mouth, sticky saliva and social eating (p < 0.001 for all three). Conclusion: Problems and symptoms during and postoncologic treatment seem to differ between women and men, which must be taken into consideration by healthcare and dental professionals. Patients with hyposalivation posttreatment have more problems and symptoms and are therefore in greater need of supportive care.