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Weight loss is a significant health problem among patients with head and neck cancer (HNC) that is attributable primarily to the tumor or tumor therapy. Critical weight loss (CWL) is defined as the unintentional loss of ≥5% of weight. Therefore, this study's goal was to investigate and determine the possible factors influencing CWL among patients with HNC who have received radiotherapy or concurrent chemoradiotherapy (CCRT). We conducted a retrospective analysis of 175 patients who received radiotherapy or CCRT as either their primary, adjuvant, or combined treatment at the Oncology Center in King Abdullah Medical City. All patients were ≥18 years of age and diagnosed with HNC with no metastasis. The study results showed that 107 patients (61%) had CWL, while 68 (39%) did not. The following factors were significantly predictive of CWL with a multivariate regression analysis: pretreatment BMI (AOR = 1.1, 95% CI = 1.02-1.17), oral cavity cancer (AOR = 10.36, 95% CI = 1.13-94.55), and male sex (AOR = 3.15, 95% CI = 1.39-7.11). In conclusion, weight loss is highly prevalent among HNC patients during treatment. Accordingly, pretreatment BMI, cancer in the oral cavity, and being male can be considered predictive factors for CWL.