Non-alcoholic fatty liver disease (NAFLD) can progress from steatosis to non-alcoholic steatohepatitis (NASH) characterized by liver inflammation, possibly leading to cirrhosis and hepatocellular carcinoma (HCC). Mice with impaired macrophage activation, when fed a high-fat diet, develop severe NASH. Evidence is mounting that Kupffer cells are implicated. However, it is unknown whether the resident CD68 ⁺ or bone marrow-derived CD11b ⁺ Kupffer cells are involved. Characterization of the FSP1cre-Pparb/d ^- ^/ ^- mouse liver revealed that FSP1 is expressed in CD11b ⁺ Kupffer cells. Although these cells only constitute a minute fraction of the liver cell population, Pparb/d deletion in these cells led to remarkable hepatic phenotypic changes. We report that a higher lipid content was present in postnatal day 2 (P2) FSP1cre-Pparb/d ^- ^/ ^- livers, which diminished after weaning. Quantification of total lipids and triglycerides revealed that P2 and week 4 of age FSP1cre-Pparb/d ^-/- livers have higher levels of both. qPCR analysis also showed upregulation of genes involved in fatty acid β-oxidation, and fatty acid and triglyceride synthesis pathways. This result is further supported by western blot analysis of proteins in these pathways. Hence, we propose that FSP1cre-Pparb/d ^-/- mice, which accumulate lipids in their liver in early life, may represent a useful animal model to study juvenile NAFLD.