This study compared the efficacy and tolerability of three enteral formulas in critically ill patients with COVID-19 who were ventilated and prone position. Enteral formulas: a) immunomodulatory (IMM), b) ω3 (ω3) and c) maltodextrins (MD). Primary outcome was percentage of patients who received both 80% of their protein and calorie targets at 3 days after enrolment. Secondary, mechanical ventilation-free time (MVF), ICU mortality, and markers of nutritional status. Tolerance of enteral nutrition (EN) was evaluated by diarrhea and gastroparesis rate. 231 patients were included, primary outcome achieved was in ω3 group (76.5% vs 59.7% and 35.2%, p < 0.001) vs IMM and MD groups. MVF were longer in ω3 and MD groups 23.11 ± 34.2 hours and 22.59 ± 42.2 hours vs IMM group 7.9 ± 22.6 hours (p < 0.01). Prealbumin final was 20.3 ± 10.8 mg/dL and 20.3 ± 9.5 mg/dL in IMM and ω3 groups vs 16.4 ± 7.0 mg/dL (p < 0.01) MD group. Transferrin were 151.5 ± 53.6 mg/dL and 152.1 ± 50.0 mg/dL in IMM and ω3 groups vs 133.7 ± 48.3 mg/dL (p < 0.05) MD group. Increase of lymphocytes was greater in ω3 1056.7 ± 660.8 cells/mm3 vs 853.3 ± 435.9 cells/mm3 and 942.7 ± 675.4 cells/mm3 (p < 0.001) IMM and MD groups. Diarrhea and gastroparesis occurred in 5.1% and 3.4% respectively. The findings of this study indicate that EN is a safe and well-tolerated intervention. The ω3 formula compared to IMM and MD did improve protein and calorie targets.