Ketogenic diets are a popular alternative to traditional dietary guidelines for individuals looking to improve body composition and metabolic health. Very low dietary carbohydrate intake (<50 g/day) increases fat oxidation and ketogenesis, even during isoenergetic conditions, compared with higher-carbohydrate diets. Rapid hormonal adaptions to the ketogenic diet involve reductions in insulin and leptin within the first 24-h that reflect integrated homeostasis and dynamic shifts in substrate oxidation. Hepatic ketogenesis and the associated increases in mitochondrial fat oxidation are oxygen-costly processes, which may explain why sleeping energy expenditure increases at the onset of a ketogenic diet. The effects on sleeping energy expenditure measured using indirect calorimetry dissipate after a few weeks of diet, whereas physical activity energy expenditure is not meaningfully altered, suggesting that energy expenditure is at least maintained in the long-term. Strategies to increase ketogenic flux at the onset of a ketogenic diet may divert stored hepatic triglyceride towards oxidation, with potential implications for metabolic dysfunction-associated steatotic liver disease (MASLD), but more work needs to be done to understand the metabolic mechanisms.