Purpose:To help identify molecular mechanisms and pathways potentially involved in the developmental toxicity for fish exposed to Deepwater Horizon (DWH) oil, transcriptomic profiles in mahi-mahi (Coryphaena hippurus) embryos exposed to different DWH oils (source and artificially weathered oil) were evaluated at different critical windows of development using High Throughput Sequencing (HTS). Methods:Total mRNA profiles of 24, 48, 96 hpf mahi-mahi larvae after slick and source oil exposure were generated by deep sequencing, in triplicate, using Illumina HiSeq2500. qRT–PCR validation was performed using SYBR Green assays. Results: Exposure to slick oil induced more pronounced changes in gene expression over time than did exposure to source oil. Predominant transcriptomic responses included alteration of E1F2 signaling, steroid biosynthesis, ribosome biogenesis, perturbation in eye development and peripheral nervous, and activation of P450 pathway. Comparisons of changes of cardiac / Ca2+-associated genes with phenotypic responses revealed reduced heart rate and increased pericardial edema in larvae exposed to slick oil but not source oil. Overall design: Total mRNA profiles of 24, 48, 96 hpf mahi-mahi larvae after slick and source (mass) oil exposure were generated by deep sequencing, in triplicate, using Illumina HiSeq2500.