Sepsis induces significant metabolic changes, including stress hyperglycemia, muscle catabolism, and increased amino acid recycling, leading to accelerated hepatic glucose production and insulin resistance. These processes are associated with mitochondrial dysfunction, reduced oxygen utilization, and impaired nutrient use. Early nutrition in sepsis can increase oxidative stress and inhibit autophagy, a cellular mechanism essential for resolution of infection. The amount and timing of nutrition is therefore critical in sepsis, with permissive underfeeding emerging as an effective strategy in the early stages of sepsis, potentially leading to fewer complications and improved outcomes. Protein intake during this early critical phase of the disease appears to play an important role in regulating autophagy and therefore requires special attention and must be managed very carefully, as excessive early protein intake may be detrimental. Recent guidelines recommend early enteral nutrition once hemodynamic stability has been achieved, but parenteral nutrition may be equally safe and may be necessary if enteral nutrition fails. The use of specific macronutrient supplements, such as omega-3 fatty acids and vitamin C, remains under investigation, with current guidelines favoring omega-3 supplementation for its anti-inflammatory effects. In conclusion, nutritional therapy in sepsis requires a balanced approach, emphasizing gradual introduction of nutrition and careful monitoring of calorie and protein intake, with supplementation strategies tailored to individual patient needs.