OBJECTIVE To investigate whether platelet counts are associated with clinical outcomes in patients with acute fatty liver of pregnancy (AFLP). METHODS We retrospectively analyzed 140 patients with AFLP admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 2010 and August 2022. In this cohort study, we used smooth curve fitting, Kaplan-Meier analysis, and multivariable logistic regression analysis to examine the independent relationship between platelet counts and 42-day postpartum mortality in AFLP. RESULTS There were 140 patients with AFLP, of which 15 died and 53 (37.86%) had thrombocytopenia. The overall 42-day postpartum maternal mortality was 10.7%. We observed a U-shaped relationship between the platelet counts and 42-day postpartum mortality. Two different slopes were observed below and above the inflection point at approximately 220 × 109 /L. After adjusting for some confounders, patients with thrombocytopenia (<100 × 109 /L) were found to have increased 42-day postpartum mortality compared with middle-tertile and highest-tertile patients. Patients with thrombocytopenia had a higher 42-day postpartum mortality, and higher proportions of intensive care unit admissions, postpartum hemorrhage, and multiple organ failure (P < 0.05). CONCLUSIONS A U-shaped association between platelet counts and 42-day postpartum mortality was observed in patients with AFLP. Thrombocytopenia is associated with poorer adverse clinical outcomes in women with AFLP.