Low and high plasma glutamine levels are associated with increased mortality. This study aimed to measure glutamine levels in critically ill patients admitted to the intensive care unit (ICU), correlate the glutamine values with clinical outcomes, and identify proxy indicators of abnormal glutamine levels. Patients were enrolled from three ICUs in South Africa, provided they met the inclusion criteria. Clinical and biochemical data were collected. Plasma glutamine was categorized as low (<420 µmol/L), normal (420-700 µmol/L), or high (>700 µmol/L). Three hundred and thirty patients (median age 46.8 years, 56.4% male) were enrolled (median APACHE II score) 18.0 and SOFA) score 7.0). On admission, 58.5% had low (median 299.5 µmol/L) and 14.2% high (median 898.9 µmol/L) plasma glutamine levels. Patients with a diagnosis of polytrauma and sepsis on ICU admission presented with the lowest, and those with liver failure had the highest glutamine levels. Admission low plasma glutamine was associated with higher APACHE II scores (p = 0.003), SOFA scores (p = 0.003), C-reactive protein (CRP) values (p < 0.001), serum urea (p = 0.008), and serum creatinine (p = 0.023) and lower serum albumin (p < 0.001). Low plasma glutamine was also associated with requiring mechanical ventilation and receiving nutritional support. However, it was not significantly associated with length of stay or mortality. ROC curve analysis revealed a CRP threshold value of 87.9 mg/L to be indicative of low plasma glutamine levels (area under the curve (AUC) 0.7, p < 0.001). Fifty-nine percent of ICU patients had low plasma glutamine on admission, with significant differences found between diagnostic groupings. Markers of infection and disease severity were significant indicators of low plasma glutamine.