Visceral leishmaniasis, caused by Leishmania donovani is characterized by clinicopathological features like hepatomegaly with loss of liver function, etc. Albumin is an essential parameter of liver function, performing various tasks like maintaining osmotic balance in blood vessels, preventing tissue fluid leakage, carrier properties, etc. Human VL patients and Leishmania donovani-infected hamsters (ExVL) were tested for their albumin levels. IL-10 derived from Leishmania donovani-infected monocytes and recombinant IL-10 were tested on HepG2 cells for CEBP-β and albumin expression with IL-10 blocking and JAK1/STAT3 inhibition. CEBP-β binding onto the albumin promoter and its silencing were performed to confirm its role in albumin expression. Low albumin, i.e., hypoalbuminemia, was found in visceral leishmaniasis and ExVL. Its levels were inversely associated with parasitic load and hepatic IL-10 in both models. When treated with Leishmania donovani-driven IL-10 from the infected monocytes and recombinant IL-10, there was a significant decrease in albumin expression from HepG2 cells in a JAK1/STAT3-dependent manner. To further explore the molecular mechanism behind hypoalbuminemia in Visceral leishmaniasis, CEBP-β, a transcription factor having three isoforms (LAP1, LAP2, and LIP), was shown to increase upon recombinant IL-10 treatment and bind to the D site of the albumin promoter using Chromatin immunoprecipitation PCR. shRNA silencing results confirm CEBP-β-mediated decrease in albumin levels. Our findings showed that increased hepatic IL-10 upon Leishmania donovani infection reduces albumin levels in a JAK1/STAT3 and CEBP-β-dependent manner.