Carnitine deficiency has been implicated as a potential pathway for cancer-related fatigue that could be treated with carnitine supplementation. The aim of this systematic literature review and meta-analysis was to evaluate the literature regarding the use of supplemental carnitine as a treatment for cancer-related fatigue.Using the PRISMA guidelines, an electronic search of the Cochrane Library, MEDLINE, Embase, CINAHL and reference lists was conducted. Data were extracted and independently assessed for quality using the Academy of Nutrition and Dietetics evidence analysis by two reviewers. In studies with positive quality ratings, a meta-analysis was performed using the random-effects model on Carnitine and cancer-related fatigue.Twelve studies were included for review with eight reporting improvement in measures of fatigue, while four reported no benefit. However, many studies were non-randomized, open-label and/or used inappropriate dose or comparators. Meta-analysis was performed in three studies with sufficient data. Carnitine did not significantly reduce cancer-related fatigue with a standardized mean difference (SMD) of 0.06 points ((95% CI -0.09, 0.21); p = 0.45).Results from studies with lower risk of bias do not support the use of carnitine supplementation for cancer-related fatigue.