Aim: Critical ill patients experience catabolic stress which results in the systemic inflammatory response. The inflammatory response is associated with increased complications including infection, multi-organ dysfunction, increased length of ICU stays, and mortality. L-Carnitine supplementation may play an important role in these patients by regulating inflammatory cell function. The purpose of the present study was to investigate the effect of L-Carnitine supplementation on clinical status, inflammatory markers, and mortality rate in critically ill patients admitted in the intensive care unit(ICU) Methods: This randomized, double-blind, placebo-controlled trial was performed on critically ill patients. Subjects were randomly assigned into placebo (n=27) and L-Carnitine (n=27) groups. L-Carnitine (3000mg/day) was administered via nasogastric tube for the intervention group for 7 days while the other group received a placebo for the same duration. Serum levels of inflammatory markers including C-reactive protein (CRP) and interleukin-6 (IL-6) were measured. Nutritional status and the acute physiology and chronic health evaluation (APACHE) score, sequential organ failure assessment (SOFA) score, and 28-day mortality were also recorded. Results: Fifty-one critically ill patients completed the study. L-Carnitine supplementation significantly reduced the levels of CRP (mean change± SE: -34.9 ± 6.5) and IL-6 (mean change ±SE: -10.64 ± 2.16) compared to the baseline, which are both statistically significant compared with the control group (p<0.05). The SOFA and APACHE scores were significantly reduced in the L-Carnitine group compared with the placebo group (p=0.02 and p<0.001, respectively). Conclusions: L-Carnitine supplementation has substantial beneficial effects on inflammatory and clinical outcomes of critically ill patients.