Terrestrial exoplanets such as TRAPPIST-1e will be observed in a new capacity with the JWST/Near Infrared Spectrograph (NIRSpec), which is expected to be able to detect CO2, CH4, and O2 signals, if present, with multiple coadded transit observations. The CO2-CH4 pair in particular is theorized to be a potential biosignature when inferred to be in chemical disequilibrium. Here, we simulate TRAPPIST-1e’s atmosphere using the ExoCAM general circulation model, assuming an optimistic haze-free, tidally locked planet with an aquaplanet surface, with varying atmospheric compositions from 10−4 bar to 1 bar of partial CO2 pressure with 1 bar of background N2. We investigate cases both with and without a modern Earth-like CH4 mixing ratio to examine the effect of CO2 and CH4 on the transmission spectrum and climate state of the planet. We demonstrate that in the optimistic haze-free cloudy case, H2O, CO2, and CH4 could all be detectable in less than 50 transits within an atmosphere of 1 bar N2 and 10 mbar CO2 during JWST’s lifespan with NIRSpec as long as the noise floor is ≲10 ppm. We find that in these optimistic cases, JWST may be able to detect potential biosignature pairs such as CO2-CH4 in TRAPPIST-1e’s atmosphere across a variety of atmospheric CO2 content, and that temporal climate variability does not significantly affect spectral feature variability for NIRSpec PRISM.