The Blue Crab, Callinectes sapidus, is a commercially, culturally, and ecologically significant species in the Gulf of Mexico (GOM), whose offshore stages were likely impacted by the Deepwater Horizon oil spill (DWH). To test for DWH effects and to better understand the planktonic ecology of this species, we monitored Callinectes spp. megalopal settlement and condition at sites within and outside of the spill extent during and one year after the DWH. We tested for DWH effects by comparing 2010 settlement against baseline data available for two sites, and by testing for differences in settlement and condition inside and outside of the spill extent. We also developed time series models to better understand natural drivers of daily settlement variation (seasonal and lunar trends, hydrodynamics, wind) during 2010 and 2011. Overall, we found that neither megalopal settlement nor body weight were significantly reduced at oiled sites, but that high unexplained variation and low statistical power made detection of even large effects unlikely. Time series models revealed remarkably consistent and relatively strong seasonal and lunar trends within sites (explaining on average 28% and 9% of variation, respectively), while wind and hydrodynamic effects were weak (1–5% variation explained) and variable among sites. This study provides insights into DWH impacts as well as the natural drivers of Callinectes spp. megalopal settlement across the northern GOM.