The TRAPPIST-1 system, consisting of an ultracool host star having seven known Earth-sized planets, will be a prime target for atmospheric characterization with the James Webb Space Telescope (JWST). However, the detectability of atmospheric molecular species may be severely impacted by the presence of clouds and/or hazes. In this work, we perform 3D general circulation model (GCM) simulations with the LMD-G model supplemented by 1D photochemistry simulations at the terminator with the Atmos model to simulate several possible atmospheres for TRAPPIST-1e, 1f, and 1g: (1) modern Earth, (2) Archean Earth, and (3) CO2-rich atmospheres. The JWST synthetic transit spectra were computed using the GSFC Planetary Spectrum Generator. We find that the TRAPPIST-1e, 1f, and 1g atmospheres, with clouds and/or hazes, could be detected using JWST’s NIRSpec Prism from the CO2 absorption line at 4.3 ?m in less than 15 transits at 3? or less than 35 transits at 5?. However, our analysis suggests that other gases would require hundreds (or thousands) of transits to be detectable. We also find that H2O, mostly confined in the lower atmosphere, is very challenging to detect for these planets or similar systems if the planets’ atmospheres are not in a moist greenhouse state. This result demonstrates that the use of GCMs, self-consistently taking into account the effect of clouds and subsaturation, is crucial to evaluate the detectability of atmospheric molecules of interest, as well as for interpreting future detections in a more global (and thus robust and relevant) approach.