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A previously healthy young female of Southeast Asian descent presented with a two-week history of polyarthritis, urticarial rash, sore throat, and 8.6 kg of unintentional weight loss. The initial workup revealed a positive parvovirus B19 polymerase chain reaction with hyperferritinemia. The patient was diagnosed with adult-onset Still's disease (AOSD) secondary to parvovirus B19 infection. Bone marrow biopsy also showed evidence of hemophagocytic lymphohistiocytosis. Viral and bacterial infections may trigger AOSD in genetically susceptible hosts either via an unknown mechanism or by direct cytotoxic effect. This case shows an atypical presentation of AOSD, as well as the challenge in diagnosing and treating AOSD complicated by macrophage activation syndrome refractory to standard treatment., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Esmaeili-Ghahfarokhi et al.)