Background: To date, there are only sporadic reports of acute abdomen and appendicitis in children with coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C). Methods: Children 17 years of age or younger assessed in 5 Latin American countries with a diagnosis of microbiologically confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and children fulfilling MIS-C definition were included. For children with acute abdomen, we investigate main radiologic patterns, surgical treatment and intraoperative findings, outcomes. Findings: One-thousand ten children were enrolled. Forty-two children (4.2%) had a clinical diagnosis of acute abdomen. Four (9.5%) were diagnosed with MIS-C and did not undergo surgery. The remaining 38 children (3.8%) underwent abdominal surgery due to suspected appendicitis, 34 of them (89.7%) had an intraoperative diagnosis of acute appendicitis (AA), while 4 of them had nonsurgical findings. Eight children died (0.8%), none of them being diagnosed with appendicitis. Children with AA were significantly older than those without (P < 0.0001). Children with complicated appendicitis had more frequently fever (85.7% vs. 60%), intestinal distension on the abdominal radiograph (7.1% vs. none), leukocytosis (85.7% vs. 40%) and high levels of C-reactive protein (35.7% vs. 5%), although differences were not statistically significant. Conclusions: Our study showed that children may present with acute abdomen during COVID-19 or MIS-C, which is not always associated with intraoperative findings of appendicitis, particularly in case of MIS-C. Further studies are needed to better characterize children with acute abdomen during COVID-19 or MIS-C, to avoid delay in diagnosis of surgical conditions and at the same time, minimize unnecessary surgical approaches.