Background: Multisystem inflammatory syndrome in children (MIS-C) is a novel pediatric disorder associated with coronavirus disease 2019. However, no laboratory parameters can diagnose MIS-C. This study aimed to determine the changes in mean platelet volume (MPV) and investigate its relationship with cardiac involvement in MIS-C. Methods: In this single-center retrospective study, 35 children with MIS-C, 35 healthy children and 35 febrile children were enrolled. Patients with MIS-C were further subdivided depending on the presence of cardiac involvement. For all patients, the white blood cell, absolute neutrophil, absolute lymphocyte, platelet counts, MPV and C-reactive protein levels were recorded. Ferritin, D-dimer, troponin and CK-MB levels and the day when IVIG was administered were recorded and compared between groups. Results: Thirteen patients with MIS-C had cardiac involvement. The mean MPV of the MIS-C group was significantly higher than those of the healthy (P = 0.0001) and febrile (P = 0.027) groups. Using a cutoff of >7.6 fL, the MPV had a sensitivity of 82.86% and specificity of 82.75%, and the area under the MPV receiver operating characteristics curve was 0.896 (0.799-0.956). The MPV was significantly higher in patients with cardiac involvement than in those without (P = 0.031). Logistic regression analysis revealed that the association between the MPV and cardiac involvement was significant (odds ratio, 2.28; 95% confidence interval, 1.04-2.95; P = 0.039). Conclusions:The MPV may indicate cardiac involvement in patients with MIS-C. Large cohort studies are needed to define an accurate cutoff value for the MPV.