The infrared imager onboard the Geostationary Operational Environmental Satellite 15 (GOES-15) provides temporally continuous observations over a limited spatial domain. To quantify bias of the GOES-15 imager, observations from four infrared channels (2, 3, 4, and 6) are compared with simulations from the numerical weather prediction model and radiative transfer model. One-day clear-sky infrared observations from the GOES-15 imager over an oceanic domain during nighttime are selected. Two datasets, Global Forecast System (GFS) analysis and ERA-Interim reanalysis, are used as inputs to the radiative transfer model. The results show that magnitudes of biases for the GOES-15 surface channels are approximately 1 K using two datasets, whereas the magnitude of bias for the GOES-15 water vapor channel can reach 5.5 K using the GFS dataset and 2.5 K using the ERA dataset. The GOES-15 surface channels show positive dependencies on scene temperature, whereas the water vapor channel has a weak dependence on scene temperature. The strong dependence of bias on sensor zenith angle for the GOES-15 water vapor channel using GFS analysis implies large biases might exist in GFS water vapor profiles.