In this study, we report molecular and metabolic responses of Sciaenops ocellatus during an acute oil exposure bioassay (100, 800 and 8000mg 1-1 of crude oil). The global DNA methylation and expression profiles of key genes of the xenobiotic biotransformation system (cytochrome P450 1A [cyp1a] and glutathione S-tranferase [gst]), oxidative stress system (glutathione peroxidase [gpx], catalase [cat], aldehyde dehydrogenase [aldh]) and reproductive system (vitellogenin [vtg]) were evaluated. At the metabolic level, we evaluated the concentration of four polycyclic aromatic hydrocarbon (PAH) metabolites -hydroxybenzo[a]pyrene, hydroxypyrene, hydroxynaphthalene and hydroxyphenanthrene- in fish bile. The results of this study revealed that fish exposed to crude oil exhibited hypomethylation of DNA, up-regulation of cyp1a and gst and down-regulation of gpx, cat, aldh and vtg and high concentrations of PAH metabolites with respect to the control.