Abstract Introduction Surgery is one of the most frequently used options in the treatment of head and neck squamous cell carcinoma. In surgical patients, the use of arterial lactate to assess hypoxemia and severe inflammatory states is well-founded. However, there are few studies on its use in patients with head and neck squamous cell carcinoma. The aim of this study was to investigate whether the serum arterial lactate level on the 1st postoperative day would be a predictor of postoperative complications in head and neck squamous cell carcinoma surgeries. Methods This is a prospective cohort, which evaluated 44 adult patients of both genders, with HNSCC, who underwent surgery associated with monobloc neck dissection as an initial treatment. Patients were divided into two groups, according to the presence or absence of postoperative complications: with complication (Clavien-Dindo II-V) and without complications (Clavien-Dindo 0-I). Student’s t-test and its variants were used to compare continuous data. Pearson’s or Spearman’s test was used to correlate the data and p values <0.05 were considered statistically significant. Results A total of 59% of the patients (n = 26/44) developed postoperative complications. Serum lactate was significantly higher in the group with complications when compared to patients without complications, respectively 2.15 mmoL/L (1.10-3.90) and 1.59 mmoL/L (0.70-3.44); p = 0.03. The prognostic accuracy of arterial lactate was 69% (95% CI: 54%-82%; p = 0.03), estimated by the ROC curve. A cut-off >1.7 mmoL/L was identified, with a sensitivity of 65.38% and specificity of 66.67%. Conclusion Arterial lactate measured on the first postoperative day is a good predictor of postoperative complications in patients with head and neck squamous cell carcinoma.