Pediatric inflammatory multisystem syndrome temporally associated with COVID-19/multi-system inflammatory syndrome in children (PIMS-TS/MIS-C) is a potentially life-threatening complication of SARS-CoV-2 infection in children. Gastrointestinal manifestations are prominent in children with PIMS-TS/MIS-C. Thus, it is challenging to differentiate this condition from an exacerbation of inflammatory bowel disease (IBD). We aimed to present the clinical characteristics, and diagnostic and therapeutic difficulties in patients with overlapping IBD and PIMS-TS/MIS-C; Methods: We reviewed medical records of children hospitalized due to overlapping IBD and PIMS-TS/MIS-C in a single pediatric hospital from December 2020 to December 2021; Results: There were four children with overlapping IBD flare and PIMS-TS/MIS-C. In three cases, IBD recognition preceded PIMS-TS/MIS-C onset and PIMS-TS/MIS-C occurred during anti-inflammatory therapy of IBD. All children presented with gastrointestinal symptoms at PIMS-TS/MIS-C onset. All patients received IVIG and ASA treatment. In three children there was a need to use steroids to resolve PIMS-TS/MIS-C symptoms. One child was vaccinated against COVID-19; Conclusions: SARS-CoV-2 infection may affect patients with underlying inflammatory conditions such as IBD, inducing systemic symptoms of PIMS-TS/MIS-C, and probably triggering IBD after PIMS-TS/MIS-C. The resemblance of clinical presentations is the main source of diagnostic and therapeutic challenges in PIMS-TS/MIS-C in patients with underlying IBD.