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Little is known about metabolic and nutrition characteristics of patients with coronavirus disease 2019 (COVID-19) and persistent critical illness. We aimed to compare those characteristics in patients with PCI and COVID-19 and patients without COVID-19 infection (non-CO)-primarily, their energy balance. This is a prospective observational study including two consecutive cohorts, defined as needing intubation for >10 days. We collected demographic data, severity scores, nutrition variables, length of stay, and mortality. Altogether, 104 patients (52 per group) were included (59 ± 14 years old [mean ± SD], 75% men) between July 2019 and May 2020. SAPSII, Nutrition Risk Screening (NRS) score, proportion of obese patients, duration of intubation (18.2 ± 11.7 days), and mortality rates were similar. Patients with COVID-19 (vs non-CO) had lower SOFA scores (P = 0.013) and more frequently needed prone position (P < 0.0001) and neuromuscular blockade (P < 0.0001): lengths of ICU (P = 0.03) and hospital stays were shorter (P < 0.0001). Prescribed energy targets were below those of the ICU protocol. The energy balance of patients with COVID-19 was significantly more negative after day 10. Enteral nutrition (EN) started earlier (P < 0.0001). During the first 10 days, COVID-19 patients received more lipid (propofol sedation) and less protein. Higher admission C-reactive protein (P = 0.002) decreased faster (P < 0.001). Whereas intestinal function was characterized by constipation in both groups during the first 10 days, diarrhea was less common in patients with COVID-19 thereafter. Compared with non-CO patients, COVID-19 patients were not more obese, had lower SOFA scores, and were fed more rapidly with EN, because of a more normal gastrointestinal function possibly due to fewer non-respiratory organ failures: their energy balances were more negative after the first 10 days. Propofol sedation reduced protein delivery.