The Sinocyclocheilus represents a rare, freshwater teleost genus endemic to China that comprises the river-dwelling surface fish and the cave-dwelling cavefish. Using a combinatorial approach of quantitative lipidomics and mass-spectrometry imaging (MSI), we demonstrated that neural compartmentalization of lipid distribution and lipid metabolism are associated with the evolution of troglomorphic traits in Sinocyclocheilus. Attenuated DHA biosynthesis via the Δ4 desaturase pathway led to reductions in docosahexaenoic acid (DHA)-phospholipids in cavefish cerebellum. Instead, cavefish accumulates arachidonic acid (ARA)-phospholipids that may disfavor retinotectal arbor growth. Importantly, MSI of sulfatides, coupled with immunostaining of myelin basic protein and transmission electron microscopy images of hindbrain axons revealed demyelination in cavefish raphe serotonergic neurons. Demyelination in cavefish parallels the loss of neuroplasticity governing social behavior such as aggressive dominance. Outside the brain, quantitative lipidomics and qRT-PCR revealed systemic reductions in membrane esterified DHAs in the liver, attributed to suppression of genes along the Sprecher pathway (elovl2, elovl5, acox1). Development of fatty livers was observed in cavefish, likely mediated by an impeded mobilization of storage lipids, as evident in the diminished expressions of pnpla2, lipea, lipeb, dagla and mgll; and suppressed β-oxidation of fatty acyls via both mitochondria and peroxisomes, reflected in the reduced expressions of cpt1ab, hadhaa, cpt2, decr1 and acox1. These neurological and systemic metabolic adaptations serve to reduce energy expenditure, forming the basis of recessive evolution that eliminates non-essential morphological and behavioral traits, giving cavefish a selective advantage to thrive in caves where proper resource allocation becomes a major determinant of survival.