Climatic drying is predicted for many tropical forests yet models remain poorly parameterized for these ecosystems, hampering predictions of forest-climate interactions. We applied an integrated model-experiment approach, parameterizing an ecosystem model with tropical forest observational data and comparing model predictions to a field drying manipulation. We hypothesized that drying suppresses soil CO2 fluxes (i.e., respiration) in relatively dry tropical forests but increases CO2 fluxes in wetter tropical forests by alleviating anaerobiosis. We measured soil CO2 fluxes during wet-dry cycles from 2015 to 2022 in four Panamanian forests that vary in rainfall and soil fertility. Measured soil CO2 fluxes declined in the dry season and peaked in the early wet season ahead of peak soil moisture, resulting in lower soil moisture optima for respiration than previously modeled. We then parameterized the model using field data and the new moisture-respiration response functions. The updated model predicted increased soil CO2 fluxes with drying in wetter and fertile forests and suppressed fluxes in drier, infertile forests. In contrast to model predictions, a chronic throughfall exclusion experiment initially suppressed soil respiration across forests, with sustained suppression for four years in the wettest forest only (-28% +/- 4% during the dry season). In the fertile forest, drying eventually elevated CO2 fluxes over this period (+75% +/- 28% during the late wet season). The unexpected negative drying effect in the wettest, infertile forest could have resulted from reduced vertical flushing of nutrients into soils. Including hydro-nutrient interactions in ecosystem models could improve predictions of tropical forest-climate feedbacks. Plain Language Summary Tropical forests are predicted to get drier with climate change over much of the globe. These forests hold some of the largest carbon stocks on Earth, so the effects of drying are significant to global climate change. We assessed effects of natural seasonal drying, and a rainfall reduction experiment, on soil CO2 fluxes (i.e., carbon losses via respiration) from four distinct tropical forests in Panama. We found that natural seasonal drying reduced soil CO2 fluxes. Using this data in an ecosystem model, we predicted that future drying will increase soil CO2 fluxes from more fertile and wetter tropical forests, where soils are often water logged, but will decrease soil CO2 fluxes from drier forests, where dry soils already suppress microbial and root activity. In contrast to these predictions, our rainfall reduction experiment showed that drying suppressed soil CO2 fluxes from the wettest forest, suggesting that not all of the important processes were represented in the model. We suggest that ecosystem models could be improved by including rainfall flushing of carbon and nutrients into soils from above, in addition to direct effects of soil moisture on respiration. Representing these processes could alter predictions of how tropical forests will respond to climatic drying.