An ongoing research program has investigated the impacts of the Deepwater Horizon oil spill (DWHOS) on the oceanic midwaters of the Gulf of Mexico (GoM), the first, largest, and longest affected ecosystem. Prior to DWHOS there was no inventory of the bathypelagial (>1000 m depth ) and that of the mesopelagial (200-1000 m) was largely restricted to the eastern GoM. Extensive sampling and analysis (2010-present) has revealed an exceptionally diverse fish assemblage with inherent pelagic endemicity. Of the 794 fish species identified to date, 180 are new records for the GoM, including one newly described and 21 putative undescribed species. This increases the total fish species number for the entire GoM by over 10%. Over half of all known fish species use the oceanic habitat for part or all of their lives. The GoM now ranks among the most-speciose oceanic ecosystems known in the World Ocean. Despite extensive sampling, the species accumulation curve has not reached asymptote; more species will likely be recorded with more sampling. This study emphasizes the increasing ‘exploitation before exploration’ trend in the deep ocean, making damage assessment highly problematic. Deep-pelagic quantitative baselines are essential in order to characterize natural variability, allowing detection of anthropogenic impacts.