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Background: Most infants infected with Toxoplasma gondii are completely asymptomatic at birth, yet they may develop ocular and neurological sequelae in the first few months of life. Cases of congenital toxoplasmosis with severe jaundice early after birth combined with pancytopenia and splenomegaly are extremely rare. Here, we report on a rare case of congenital toxoplasmosis presenting with severe jaundice and hemolysis early after birth combined with pancytopenia and splenomegaly.Case Presentation: A male preterm infant with severe jaundice and splenomegaly was admitted to our department. Laboratory examinations revealed severe hyperbilirubinemia, increased reticulocytes, and pancytopenia. After comprehensive analysis and examination, the final diagnosis was congenital toxoplasmosis, and the infant was treated with azithromycin and subsequently trimethoprim-sulfamethoxazole. Regular follow-up revealed congenital toxoplasmosis in both eyes, which was surgically treated, while neurofunctional assessment results were unremarkable. In this case of congenital toxoplasmosis combined with severe jaundice, we treated the infant with two courses of azithromycin, followed by trimethoprim-sulfamethoxazole after the jaundice resolved. Clinical follow-up indicated that this treatment was effective with few side effects; thus, this report may serve as a valuable clinical reference.Conclusions: Timely diagnosis and adequate treatment are closely associated with congenital toxoplasmosis-related prognosis. Infants with congenital toxoplasmosis require long-term follow-up, focusing on nervous system development and ophthalmology. [ABSTRACT FROM AUTHOR]