Surgical intervention for head and neck cancer has the potential to induce uncontrolled inflammation and immune suppression, which may result in tissue injury and an elevated risk of infectious complications. The immune response can be modulated, and immunonutrients can influence the progression of diseases. The study investigated the effect of adding omega 3 and Dipeptiven to standard feeding in head and neck patients undergoing oral cavity or mandibular resection. Methods: This pilot study was performed on 70 cancer patients aged from 20 to 60 years old, both sexes, undergoing hemiglossectomy with/without submental flap with body mass index between 18.5-24.9, serum albumin above 3 gm. Patients were divided into two equal groups receiving standard feeding with caloric distribution (45%-50% carbohydrates,20-35% from fats, and 10-35% from protein) in group A, plus perioperative supplementation with omega 3 and dipeptiven (immunonutrition mixture) in group B. Results: Demographic data, duration of surgery, and cancer types were comparable between both groups. Fistula formation and healing duration were significantly decreased in group B than in group A (P value=0.01). Conclusions: Immunonutrition considerably affects lowering fistula incidence in hemiglossectomy patients. Also, immonutrition lowered the healing time of this fistula.