Objectives: We aimed to measure SARS-CoV-2 serologic responses in children TRANS hospitalized with multisystem inflammatory syndrome MESHD (MIS-C) compared to COVID-19, Kawasaki Disease MESHD (KD) and other hospitalized pediatric controls. Methods: From March 17, 2020 - May 26, 2020, we prospectively identified hospitalized children TRANS at Children TRANS's Healthcare of Atlanta with MIS-C (n=10), symptomatic PCR-confirmed COVID-19 (n=10), KD (n=5), and hospitalized controls (n=4). With IRB approval, we obtained prospective and residual blood SERO samples from these children TRANS and measured SARS-CoV-2 spike (S) receptor binding domain (RBD) IgM and IgG binding antibodies SERO by quantitative ELISA SERO and SARS-CoV-2 neutralizing antibodies SERO by live-virus focus reduction neutralization assay. We statistically compared the log-transformed antibody SERO titers among groups and performed correlation analyses using linear regression. Results: All children TRANS with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies SERO, which correlated strongly with neutralizing antibodies SERO (R2=0.667, P<0.001). Children TRANS with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody SERO titers (geometric mean titer [GMT] 6800, 95%CI 3495-13231) than children TRANS with COVID-19 (GMT 626, 95%CI 251-1563, P<0.001), children TRANS with KD (GMT 124, 95%CI 91-170, P<0.001) and other hospitalized pediatric controls (GMT 85 [all below assay limit of detection], P<0.001). All children TRANS with MIS-C also had detectable RBD IgM antibodies SERO, indicating recent SARS-CoV-2 infection MESHD. RBD IgG titers correlated with erythrocyte sedimentation rate (ESR) (R2=0.512, P<0.046) and with hospital and ICU lengths of stay (R2=0.590, P=0.010). Conclusion: Quantitative SARS-CoV-2 RBD antibody SERO titers may have a role in establishing the diagnosis of MIS-C, distinguishing it from other similar clinical entities, and stratifying risk for adverse outcomes.