Resistance to ivermectin (IVM) critically undermines the efficacy of anthelmintic therapy in both animals and humans. The mechanisms driving the development of resistance to IVM in nematode parasites are complex and involve multiple factors which are far from being understood. Among these, the nuclear hormone receptor NHR-8 has recently been identified as a significant factor in both Caenorhabditis elegans and the ruminant parasitic nematode Haemonchus contortus (1). Interestingly, NHR-8 is not only described as central in protection against drugs (2), but alos it regulates lipid homeostasis in C. elegans (3). Concurrently, IVM exposure has been shown to disrupt lipid metabolism in mammalian cells (4,5) and in nematodes (6, 7). We hypothesized that IVM-resistant C. elegans would exhibit altered lipid metabolism as a result of IVM exposure and the activation of the nhr-8 regulatory cascade. We compared wild-type N2B, IVM10, and nhr-8-deficient C. elegans using complementary approaches, including imaging of triacylglycerol content via oil-red staining and Coherent anti-Stokes Raman scattering (CARS) spectroscopy. Additionally, RNA sequencing analysis was conducted to identify potential changes in gene expression. Our data indicated that triacylglycerol stores were modified in IVM-resistant C. elegans. We identified several genes with abnormal expression levels in IVM-resistant and NHR-8-deficient C. elegans, which may contribute to the observed alterations in lipid stores in IVM-resistant specimens. Altered lipid metabolism affects fitness, and the molecular targets involved in this alteration present potential avenues for countering anthelmintic resistance in parasitic nematodes.