We demonstrate the unique capability of the MODIS instruments in detecting oil slicks in an open ocean environment. On 13 May 2006, in the NW Gulf of Mexico where water depth ranges from 50 to 2500 m, one 250-m resolution MODIS image showed at least 164 surface slicks under sun glint (glint reflectance, Lg, ranged between 0.0001 and 0.06 sr−1). After discounting other possible causes, we believe these are the result of natural seeps. Our analysis showed total coverage of ∼1900 km2, with individual slicks varying in surface area (11.7 ± 14.8 km2) and length (19.2 ± 12.4 km). Concurrent SAR imagery showed similar area estimates to within 30%. This estimate, based on a single image, is higher than earlier estimates from a database of multi-date SAR images for the same region. Inspection of >200 images for the month of May between 2000 and 2008 revealed similar slicks on at least 50 images. On 2 June 2005, slicks were detected under sun glint with both negative contrast (Lg < 0.05 sr−1) and positive contrast (Lg > 0.05 sr−1). These slicks could not be detected in glint-free MODIS images collected on the same day. Because of the near-daily revisit and wide sun glint coverage (e.g., >800 km E-W between March and October at 25°N), systematic and global application of the MODIS 250-m imagery can help locate natural seeps and improve estimates of seepage rates in the world's ocean.