We examine the uncertainty in net ecosystem exchange due to the model treatment of heterotrophic respiration in a variety of hydroclimatic conditions using a land surface model. Multiple soil temperature-respiration functions and soil moisture-respiration functions are incorporated into the Carnegie-Ames-Stanford Approach with Carbon-Nitrogen-Phosphorus (CASA-CNP) biogeochemical model coupled to the Community Atmosphere Biosphere Land Exchange land surface model. Every possible combination of the newly implemented functions is then used to simulate heterotrophic respiration and net ecosystem exchange at 10 different flux towers covering a large range of global vegetation types. Results show that a large uncertainty in the simulated net ecosystem exchange is attributable to differences in the soil respiration parameterization. No single combination of soil temperature and moisture-respiration functions appears to show superior performance across all sites. Large variations in the simulated evolution of soil carbon storages emphasize the problem that to use an observationally based soil temperature or soil moisture response function requires a land surface model to capture the observed soil temperature and soil moisture mean and variability correctly. Land surface models are known to vary dramatically in their simulation of the soil moisture state and probably in their simulation of soil temperature. Resolving how to simulate heterotrophic respiration and net ecosystem exchange will therefore require an accurate simulation of temperature and moisture combined with a realistic soil heterotrophic respiration parameterization, and these cannot be developed and implemented in isolation.