This comprehensive review explores the role of antioxidants in managing sepsis-associated oxidative stress. Sepsis, a life-threatening condition characterized by organ dysfunction, affects millions globally and is a significant contributor to mortality in critical care units. The review highlights the complex interplay between infection, inflammation, and oxidative stress (OS) in the pathogenesis of sepsis. It discusses the involvement of reactive oxygen species (ROS) and their impact on cellular metabolism, immune response, and organ function. The article also examines the antimicrobial properties of various antioxidants, including vitamin E, vitamin C, melatonin, N-acetylcysteine (NAC), selenium, carnosine, and fish oil, and their potential therapeutic benefits in sepsis treatment. Additionally, the review explores the mechanisms by which antioxidants mitigate OS and their effects on mitochondrial dysfunction, inflammatory responses, and immune suppression. The findings suggest that while antioxidants can reduce oxidative damage, their efficacy in sepsis management may be influenced by their ability to modulate the inflammatory response and protect against further cellular damage. The review concludes by emphasizing the need for further research to optimize the use of antioxidants in sepsis therapy.This comprehensive review explores the role of antioxidants in managing sepsis-associated oxidative stress. Sepsis, a life-threatening condition characterized by organ dysfunction, affects millions globally and is a significant contributor to mortality in critical care units. The review highlights the complex interplay between infection, inflammation, and oxidative stress (OS) in the pathogenesis of sepsis. It discusses the involvement of reactive oxygen species (ROS) and their impact on cellular metabolism, immune response, and organ function. The article also examines the antimicrobial properties of various antioxidants, including vitamin E, vitamin C, melatonin, N-acetylcysteine (NAC), selenium, carnosine, and fish oil, and their potential therapeutic benefits in sepsis treatment. Additionally, the review explores the mechanisms by which antioxidants mitigate OS and their effects on mitochondrial dysfunction, inflammatory responses, and immune suppression. The findings suggest that while antioxidants can reduce oxidative damage, their efficacy in sepsis management may be influenced by their ability to modulate the inflammatory response and protect against further cellular damage. The review concludes by emphasizing the need for further research to optimize the use of antioxidants in sepsis therapy.