Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, characterized by an initial hyperinflammatory phase frequently followed by compensatory immunosuppression (CARS). Regulatory T cells (Tregs) play a critical, biphasic role: inadequate suppression during early hyperinflammation fails to control cytokine storms, while excessive/persistent activity in late-phase immunosuppression drives immune paralysis and secondary infection susceptibility. This review explores advances in targeting Treg immunoregulation across bacterial, viral, and fungal sepsis, where pathogenic type critically influenced the types of immunoresponses, shaping Treg heterogeneity in terms of phenotype, survival, and function. Understanding this multifaceted Treg biology offers novel therapeutic avenues, highlighting the need to decipher functional heterogeneity and develop precisely timed, pathogen-tailored immunomodulation to safely harness beneficial Treg roles while mitigating detrimental immunosuppression.