A method of performing comb-assisted spectroscopy in the 2- and 4-μm wavelength regions is deeply discussed and applied to the spectroscopic characterization of absorption lines of a CO2 gas sample. The method relies on the use of a sum-frequency-generation scheme to relate the frequency of the probing laser to a frequency comb provided by an Er:fiber femtosecond oscillator. Controlled scans of the comb repetition frequency allow highly accurate and reproducible acquisition of the absorption spectra, which are used for subsequent retrieval of the underlying spectroscopic parameters.