Objectives: To investigate the effect of our improved nursing strategy on prognosis in immunosuppressed patients with pneumonia and sepsis. Methods: Immunosuppressed patients (absolute lymphocyte count <1000 cells/mm3) with pneumonia and sepsis were enrolled and divided into a control group and treatment group. The treatment group received the improved nursing strategy. The primary outcome in this study was 28-day mortality. Results: In accordance with the study criteria, 1019 patients were finally enrolled. Compared with patients in the control group, those in the treatment group had significantly fewer days on mechanical ventilation [5 (4, 7) versus 5 (4, 7) days, P =.03] and lower intensive care unit (ICU) mortality [21.1% (132 of 627) vs 28.8% (113 of 392); P =.005] and 28-day mortality [22.2% (139 of 627) vs 29.8% (117 of 392); P =.006]. The treatment group also had a shorter duration of ICU stay [9 (5, 15) vs 11 (6, 22) days, P =.0001] than the control group. The improved nursing strategy acted as an independent protective factor in 28-day mortality: odds ratio 0.645, 95% confidence interval: 0.449-0.927, P =.018. Conclusion: Our improved nursing strategy shortened the duration of mechanical ventilation and the ICU stay and decreased ICU mortality and 28-day mortality in immunosuppressed patients with pneumonia and sepsis. Trial registration: ChiCTR.org.cn, ChiCTR-ROC-17010750. Registered 28 February 2017. [ABSTRACT FROM AUTHOR]