Up to 6% of kidney transplant recipients (KTRs) experience life-threatening complications requiring intensive care unit (ICU) admission, and one of the most common medical complications requiring ICU admission is infection. This study aimed to evaluate the effect of immunosuppressive therapy (IST) modification on prognosis of KTRs with sepsis. We conducted a multicenter retrospective study in 4 university-affiliated hospitals to evaluate the effect of adjusting the IST in KTRs with sepsis. Only patients who either maintained IST after ICU admission or those who underwent immediate (within 24 h of ICU admission) reduction or withdrawal of IST following ICU admission were included in this study. "Any reduction" was defined as a dosage reduction of any IST or discontinuation of at least 1 IST. "Complete withdrawal of IST" was defined as concomitant discontinuation of all ISTs, except steroids. During the study period, 1596 of the KTRs were admitted to the ICU, and 112 episodes of sepsis or septic shock were identified. The overall in-hospital mortality rate was 35.7%. In-hospital mortality was associated with higher sequential organ failure assessment score, simplified acute physiology score 3, non-identical human leukocyte antigen relation, presence of septic shock, and complete withdrawal of IST. After adjusting for potential confounding factors, complete withdrawal of IST remained significantly associated with in-hospital mortality (adjusted coefficient, 1.029; 95% confidence interval, 0.024-2.035) and graft failure (adjusted coefficient, 2.001; 95% confidence interval, 0.961-3.058). Complete IST withdrawal was common and associated with worse outcomes in critically ill KTRs with sepsis.