Obesity is a public health concern with rising incidence and prevalence rates. Research exploring the metabolomic biomarkers for obesity suggests a potential association between elevated acylcarnitine concentrations in individuals with obesity compared to lean controls. Low-carbohydrate (LC) and high-complex-carbohydrate (HCC) dietary patterns are commonly followed by individuals with overweight and obesity seeking to lose weight. Yet, little is known about how these diets affect circulating acylcarnitine concentrations in combination with changes in body mass, lean mass, and fat mass. The goal of this secondary analysis of data obtained from the Comparison of Health Benefits and Risks of High-Carbohydrate, Low-Fat or Very-Low-Carbohydrate Diets for Weight Loss Study was to determine the effect of LC and HCC dietary interventions on circulating acylcarnitine concentrations among healthy adults with overweight and obesity. The first aim was to describe the impact of consuming a LC or HCC diet on fasting acylcarnitine concentrations at baseline and 2, 4, 6, and 18-weeks after dietary intervention. The second aim was to define the relationships between changes in lean mass, fat mass, and fasting acylcarnitine concentrations within and between the ad libitum LC diet group and the energy-matched HCC diet group.