Oxygen is mandatory for most organisms to survive. It is used to produce energy in the form of adenosine triphosphate (ATP) during oxidative phosphorylation. While most organisms fail upon oxygen deprivation (anoxia), the Nematode Caenorhabditis elegans is able to face this stress for 48 hours. This work describes the involvement of the sphingolipid metabolism in the resistance to anoxia in this Nematode. It suggests that the accumulation of some species of sphingolipid (glucosylceramides and sphingomyelins) may have a toxic effect that could weaken the nematode in anoxic condition. It reveals that the tetratricopeptide protein (TTC-1) has an important role in maintaining the sphingolipid homeostasis and is essential to counteract the anoxia hypersensitivity found in a mutant that is depleted for its ceramide synthase (HYL-2). The depletion of TTC-1 restores a normal resistance to 48 hours of anoxia in HYL-2 mutants by avoiding the accumulation of C24/C25 glucosylceramides and C24/C25/C26 sphingomyelins.