Aims: To evaluate the impact of vitamin D status on oncologic outcomes, PDL1 expression and the Quality of life (QoL), in head and neck squamous cell carcinoma patients (HNSCC) receiving standard-of-care treatment. Methodology: In this prospective observational study (CTRI/2020/01/023049), treatment-naïve patients with HNSCC were included. The pre-treatment levels of Vitamin D were measured and corrected when deficient/insufficient. The patients received standard treatment for their cancer. PDL-1 expression was assessed in the tumour tissue, and the combined positive score (CPS) was documented. The QoL were recorded at baseline and during follow-up using FACT-HN. Results: A total of 300 were included in the final analysis. The median age of the patients was 49 years, with the majority being male (n = 243, 81%) and tobacco users (smokeless) (244, 81.3%) presenting with advanced disease (n = 203, 67.7%). Buccal Mucosa-Gingivobuccal Sulcus (BM-GBS) (n=147,49%) was the most common site. Vitamin D  20 ng/ml was seen in the large majority (n=209,69.7%). All patients underwent surgery followed by adjuvant treatment when indicated. The CPS > 10 was seen in 215 (71.7%) patients. There was no correlation between vitamin D levels and CPS score in our cohort of patients. There was also no influence of Vitamin D levels or CPS on patients DFS. Overall, the patients in this cohort were doing well in terms of their QoL, with FACT-G ≥80 and FACT-H&N ≥100. Patients with advanced cancer, especially those receiving adjuvant concurrent chemoradiotherapy, had poor QoL across domains. Conclusions: In our cohort of HNSCC patients, vitamin D levels of  20 ng/ml were highly prevalent. The CPS >10 was also high. There was no correlation between vitamin D deficiency and PDL1 expression. The overall QoL of the HNSCC patients was good.