Pneumocystis pneumonia (PCP) with hypoxic respiratory failure is increasing in human immunodeficiency virus (HIV)-negative patients. However, there is no study evaluating the effect of early anti-PCP treatment on clinical outcomes in HIV-negative patient with severe PCP. Therefore, this study investigated the association between the time to anti-PCP treatment and clinical outcomes in HIV-negative patients with PCP presented with hypoxemic respiratory failure. A retrospective observational study was performed of 51 HIV-negative patients with PCP presented with respiratory failure and admitted to the intensive care unit between October 2005 and July 2018. A logistic regression model was used to adjust for potential confounding factors in the association between time to anti-PCP treatment and in hospital mortality. All patients were treated with appropriate anti-PCP treatment, primarily with trimethoprim/sulfamethoxazole. The median time to anti-PCP treatment was 58.0 (28.0 - 97.8) hours. Thirty-one (60.8%) patients were treated empirically prior to microbiological diagnosis confirmed. However, hospital mortality rates were not associated with increasing quartiles of time to anti-PCP treatment (P = 0.818, test for trend). All patients who applied high-flow nasal cannula for respiratory support on ICU admission day survived. In a multiple logistic regression model, the time to anti-PCP treatment was not associated with increased mortality. However, age (adjusted OR 1.07, 95% CI 1.01 - 1.14) and failure to initial treatment (adjusted OR 13.03, 95% CI 2.34 - 72.65) were independently associated with increased mortality. In conclusion, there was no association between the time to anti-PCP treatment and treatment outcomes in HIV-negative patients with PCP presented with hypoxemic respiratory failure. Higher mortality rate was independently associated with respiratory failure requiring mechanical ventilation support, age, and failure of the initial anti-PCP treatment.