In this work, we report the first detailed theoretical comparative conformational investigation between two different classes of hydrofluoropolyethers: dihydro‐ and dimethoxyfluoropolyethers. The main objective was to determine a cost‐effective computational methodology that could accurately reproduce the energetic rankings and thermal weight factors of the simplest examples of those two classes calculated with M08‐HX/triple‐ζ//M08‐HX/double‐ζ benchmark model chemistries. Between the tested methodologies, M08‐HX/aug‐pcseg‐2//M08‐HX/pcseg‐1 was found to be the most appropriate, exhibiting a good accuracy and considerable reduction in computational cost with respect to the benchmark, being more than three times faster than M08‐HX/aug‐pcseg‐2//M08‐HX/aug‐pcseg‐1. This cost‐effective approach will be essential in future work when studying larger hydrofluoropolyethers, where the computational complexity associated with increasing number of conformers will require such approximations.