This review explores the role of antioxidants in sepsis-associated oxidative stress, focusing on their potential as adjuncts to primary therapies in sepsis treatment. Sepsis is a life-threatening condition caused by an imbalanced immune response to infection, leading to organ dysfunction. Increased reactive oxygen species (ROS) and exhausted antioxidant pathways contribute to sepsis pathogenesis. Antioxidants with antimicrobial properties may help mitigate the inflammatory response and support primary therapies like fluid and antibiotic treatments. The review discusses the advantages and disadvantages of antioxidant use in sepsis, highlighting their potential to act additively or synergistically on different pathways. Immunoadjuvant therapy is also considered as a promising advancement in sepsis treatment. The review covers various sepsis types, including bacterial, viral, and fungal sepsis, and their mechanisms. It also examines the role of oxidative stress in sepsis, mitochondrial dysfunction, and inflammatory reactions. Antioxidants such as vitamin E, vitamin C, and melatonin are discussed for their antimicrobial properties. N-acetylcysteine (NAC) is also highlighted for its potential in preventing biofilm formation. The review emphasizes the importance of antioxidants in mitigating cellular damage and improving clinical outcomes in sepsis.This review explores the role of antioxidants in sepsis-associated oxidative stress, focusing on their potential as adjuncts to primary therapies in sepsis treatment. Sepsis is a life-threatening condition caused by an imbalanced immune response to infection, leading to organ dysfunction. Increased reactive oxygen species (ROS) and exhausted antioxidant pathways contribute to sepsis pathogenesis. Antioxidants with antimicrobial properties may help mitigate the inflammatory response and support primary therapies like fluid and antibiotic treatments. The review discusses the advantages and disadvantages of antioxidant use in sepsis, highlighting their potential to act additively or synergistically on different pathways. Immunoadjuvant therapy is also considered as a promising advancement in sepsis treatment. The review covers various sepsis types, including bacterial, viral, and fungal sepsis, and their mechanisms. It also examines the role of oxidative stress in sepsis, mitochondrial dysfunction, and inflammatory reactions. Antioxidants such as vitamin E, vitamin C, and melatonin are discussed for their antimicrobial properties. N-acetylcysteine (NAC) is also highlighted for its potential in preventing biofilm formation. The review emphasizes the importance of antioxidants in mitigating cellular damage and improving clinical outcomes in sepsis.