Purpose: Our study aimed to quantify the impact of submandibular gland (SMG) resection during Level I neck dissection (ND) on stimulated salivary output (SSO) and xerostomia-related quality of life in patients with head and neck cancer (HNC). Methods: A retrospective cohort was formed from 32 patients that underwent unilateral or bilateral Level I ND and a control group of 23 patients that had level II-IV ND. SSO (Saxon test) and University of Washington Quality of Life survey results for both groups were compared. Results: Mean SSO was 3.41 g in the SMG resection group and 3.86 g in the control group, with no significant statistical difference. There was no difference in mean SSO between patients with 2 SMGs, a single remaining SMG, or no glands. The mean SSO of SMG resection cases with a history of adjuvant RT was 2.61 g which was below the xerostomia threshold for the Saxon test (2.75 g) and control group patients with RT had a significantly higher mean SSO (4.07 g). The lowest UW-QoL saliva domain score average (53.8) was in the SMG-resected, RT-positive group. Conclusion: Results indicate unilateral or bilateral resection of SMG does not reduce SSO to a significant extent. Adjuvant radiotherapy and SMG resection are additive risk factors for xerostomia and the related loss in quality of life. SMG sparing may be necessary in HNC patients with higher risk for the need of adjuvant radiation.