Background/Objectives: Early feeding intolerance (FI) affects 20–50% of critically ill patients receiving enteral nutrition, yet no validated predictive tool exists and diagnosis remains retrospective. Plasma citrulline, mainly synthesized by enterocytes, is considered as the “factor V of the intestine”. The citrulline generation test (CGT) evaluates small bowel mucosal function by measuring the increase in plasma citrulline after glutamine administration. We hypothesized that patients with a lower CGT would be more prone to FI. We aimed to compare CGT results according to the presence or absence of FI and to identify factors associated with CGT. Methods: This prospective study was conducted in the medical intensive care unit (ICU) of Besancon Hospital. Plasma citrulline and glutamine concentrations were measured at admission and after an alanine–glutamine dipeptide bolus. CGT was defined as the slope between basal and 90 min peak plasma citrulline concentrations. Signs of FI were collected during follow-up. Results: Among the sixty-six included patients, nine (14%) developed FI by day three, only characterized by vomiting and gastric residual volumes above 500 mL; abdominal pain or diarrhea were not observed. CGT values did not differ between patients with and without FI. CGT correlated positively with baseline citrulline and peak glutamine concentrations. Conclusions: FI was not associated with CGT, possibly because FI was predominantly gastric rather than intestinal. Low CGT values were associated with low plasma citrulline concentrations, suggesting reduced functional enterocyte mass. The positive correlation between CGT and peak plasma glutamine suggests that CGT not only reflects enterocyte function but also glutamine bioavailability.