Reactive oxygen species (ROS) are formed through various cellular processes and can cause cellular damage, leading to diseases such as aging, cancer, and neurological disorders. Mitochondrial ROS (mt-ROS) play a crucial role in regulating physiological processes and immune responses. This review focuses on the mechanisms by which mt-ROS regulate host immune responses against infections caused by bacteria, protozoans, viruses, and fungi. It also discusses how pathogens modulate mt-ROS to evade host immunity. The review concludes by discussing potential therapeutic approaches involving mt-ROS in infectious diseases. Key points: - ROS are formed by electron transfer to molecular oxygen and can be highly reactive free radicals or less reactive nonradical species. - Mitochondria are major sites for ROS generation, but other organelles and compartments can also produce ROS. - mt-ROS are primarily generated as byproducts of the electron transport chain (ETC) and participate in various physiological functions. - mt-ROS are involved in immune signaling, including T cell activation, neutrophil activation, and inflammasome activation. - Pathogens employ mechanisms to modulate mt-ROS to evade host immunity, such as inducing mitophagy or using virulence factors to suppress mt-ROS generation. - Therapeutic approaches targeting mt-ROS have shown promise in reducing oxidative stress and improving outcomes in infectious diseases.Reactive oxygen species (ROS) are formed through various cellular processes and can cause cellular damage, leading to diseases such as aging, cancer, and neurological disorders. Mitochondrial ROS (mt-ROS) play a crucial role in regulating physiological processes and immune responses. This review focuses on the mechanisms by which mt-ROS regulate host immune responses against infections caused by bacteria, protozoans, viruses, and fungi. It also discusses how pathogens modulate mt-ROS to evade host immunity. The review concludes by discussing potential therapeutic approaches involving mt-ROS in infectious diseases. Key points: - ROS are formed by electron transfer to molecular oxygen and can be highly reactive free radicals or less reactive nonradical species. - Mitochondria are major sites for ROS generation, but other organelles and compartments can also produce ROS. - mt-ROS are primarily generated as byproducts of the electron transport chain (ETC) and participate in various physiological functions. - mt-ROS are involved in immune signaling, including T cell activation, neutrophil activation, and inflammasome activation. - Pathogens employ mechanisms to modulate mt-ROS to evade host immunity, such as inducing mitophagy or using virulence factors to suppress mt-ROS generation. - Therapeutic approaches targeting mt-ROS have shown promise in reducing oxidative stress and improving outcomes in infectious diseases.