Objectives: Yellow fever virus (YFV) is a key concern in West Africa, often associated with febrile jaundice. However, many patients with this syndrome test negative for YFV, raising questions about other potential viral etiologies. This study aimed to characterize the viral landscape in YFV-negative febrile jaundice cases using metagenomic next-generation sequencing (mNGS). Methods: Serum samples were collected in 2019 from 152 febrile jaundice patients in Burkina Faso who tested negative for both YFV and malaria. A random subset of 100 samples was analyzed by mNGS to identify viral sequences. Bioinformatic pipelines were applied to classify viral reads, and findings were validated by quantitative PCR (qPCR) and serological assays. Additional specimens from the same cohort, as well as from febrile patients without jaundice, were tested to assess the prevalence of the key viral findings. Results: mNGS revealed 58 viral species, including four human pathogens: HIV-1 (n=1), YFV (n=1), hepatitis A virus (HAV, n=16), and hepatitis B virus (HBV, n=18). qPCR confirmed 75% of HAV and 67% of HBV cases. Serological testing on additional samples confirmed comparable HAV and HBV prevalence among jaundiced patients, but significantly lower rates among those without jaundice. Conclusion: mNGS uncovered undiagnosed viral infections, demonstrating its value for differential diagnosis and surveillance in resource-limited settings.