This study projected responses of forest net primary productivity (NPP) to three climate change scenarios at a resolution of 5 km × 5 km across the state of Louisiana, USA. In addition, we assessed uncertainties associated with the NPP projection at the grid and state levels. Climate data of the scenarios were derived from Community Climate System Model outputs. Changes in annual NPP between 2000 and 2050 were projected with the forest ecosystem model PnET-II. Results showed that forest productivity would increase under climate change scenarios A1B and A2, but with scenario B1, it would peak during 2011–2020 and then decline. The projected average NPP under B1 over the years from 2000 to 2050 was significantly different from those under A1B and A2. Forest NPP appeared to be primarily a function of temperature, not precipitation. Uncertainties of the NPP projection were due to large spatial resolution of the climate variables. Overall, this study suggested that in order to project effects of climate change on forest ecosystem at regional level, modeling uncertainties could be reduced by increasing the spatial resolution of the climate projections.