Introduction: Molnupiravir (MPV) is an oral, potent ribonucleoside analog that inhibits the replication of SARS-CoV-2 and is indicated for the treatment of adults with COVID-19. Patients with COVID-19 are at an elevated risk of adverse outcomes, underscoring the need for precise pharmacokinetic (PK) data to guide safe drug use. For MPV and its active metabolite, N4-hydroxycytidine (NHC), renal excretion is not the primary elimination pathway. Consequently, renal impairment has minimal impact on their PK profiles, and no dose adjustment is recommended for patients with mild to moderate renal impairment. However, there are no relevant pharmacokinetic studies in patients with severe renal insufficiency (eGFR<30 mL/min/1.73 m Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect the plasma concentrations of MPV and NHC. All analytes were extracted by protein precipitation using acetonitrile at a ratio equivalent to 3:1, and QMPV and QNHC were evaluated by calculating the ratio of plasma concentrations. Results: A total of four patients with stage 4 or 5 chronic kidney disease (CKD) were enrolled in the study. All patients received a standard oral dose of molnupiravir (MPV), and plasma samples were collected 12 h post-administration (C Conclusion: MPV was rapidly hydrolyzed to NHC in the body and maintained at a low level. The NHC is significantly higher than that of patients with mild to moderate symptoms, especially those with stage 5 chronic kidney disease. The blood drug concentration is equivalent to Cmax, which suggests that when used clinically in patients with uremia, the dosing interval should be adjusted to avoid drug accumulation and occurrence of AEs.