Introduction: Conjoined twins are a rare medical phenomenon that poses unique challenges for surgeons. Separation of conjoined twins involves multidisciplinary teamwork, complex medical management and surgical planning, and multi-stage operations and often still has a high mortality and morbidity rate. In the times of the COVID-19 pandemic, separation of conjoined twins pose even greater challenges. Aiming for the best outcome possible, while minimizing the risk of COVID transmission and ensuring the safety of the personnel, is paramount. This case report presents thoraco-omphalopagus twins who were successfully separated at 4 months of age. The preoperative planning, operative details, postoperative follow-ups, and outcomes are discussed. Methods: The absence of a tissue expander and the inability to acquire it due to travel restrictions from COVID-19 further complicated the management on this patient. A Routine Polymerase Chain Reaction (PCR) swab test was performed on the patients and personnel. Standardized personnel protective equipment (PPE) was worn during ward and surgical care. After separation of the twins by cardiothoracic and pediatric surgeons, one twin underwent immediate skin closure using a double keystone perforator island flap and a lower abdominal perforator flap. Due to extensive defects, closure was delayed for the second twin. After a series of dressing changes, eventually local perforator flaps could be raised to close the defect using staged tension sutures and skin grafts for secondary defects. Results: Both twins were discharged with no significant morbidity, and no personnel were exposed to COVID-19 infection during the management. Conclusion: Preoperative coordination and planning, multidisciplinary effort, adherence to screening protocols for COVID, and strict use of standardized PPE all contributed to the successful separation of thoraco-omphalopagus conjoined twins during the COVID-19 pandemic.