Background <p>Distress is a multifactorial emotional experience which many cancer patients experience. Increased distress levels, as measured by the NCCN distress thermometer, are associated with poor treatment compliance and reduced survival. It has also been shown to be associated with poor wound healing.</p> Methodology <p>This prospective observational was done to assess the incidence of preoperative distress levels in head and neck squamous cell carcinoma patients and its impact on postoperative complications.</p> Results <p>A total of 350 patients were enrolled in the study. The majority of the patients had oral squamous cell carcinoma (<i>n</i> = 333, 95.1%). The incidence of postoperative complications was 14.3% (<i>n</i> = 50/350). The incidence of preoperative distress levels of ≥ 4 was only 5.14% (<i>n</i> = 18/350), and it did not have any influence on the postoperative complications. The factors that predisposed to the development of postoperative complications were the need for tracheostomy (<i>p</i> &lt; 0.001 [5.844(3.060 − 11.160)]), duration of surgery &gt; 4&#xa0;h (<i>p</i> = 0.012 [3.753(1.833 − 4.807)]), and patient belonging to the lower socioeconomic strata (<i>p</i> = 0.003[2.711(1.407 − 5.224)]).</p> Conclusions <p>The incidence of significant preoperative distress levels was low in our cohort, and it did not influence the development of postoperative complications. The findings from this study may well need further confirmation. The low distress scores reported in our study should not deter from routinely checking for preoperative distress levels in head and neck cancer patients.</p>