Recently, integrated silicon photonics have attracted much interest in mid-infrared applications for many reasons, such as gas sensing. Unfortunately, traditional silicon on silica waveguides suffer from huge silica absorption losses beyond the wavelength of 3.7 μm, where the absorption fingerprint of many gases, such as carbon dioxide, exist. Also, power leakage from the waveguide core to the substrate is significant for the standard 2 μm-thick buried silica underneath the 220 nm thick silicon layer at such long wavelengths. Therefore, efforts were exerted to find alternative materials, such as sapphire and silicon nitride, which offer lower absorption while keeping a strong refractive index contrast with silicon, and hence small fabrication footprints. In this work, though, we show that an optimized design of single-mode silicon on silica waveguides could push this technology limits deeper into the mid-infrared zone. A challenging wavelength of 4.28 μm, where CO2 possesses a strong absorption peak, is chosen for this study. We show that the leakage loss can be eliminated using 5 μm and 4 μm thick buried silica layers for 220 nm and 300 nm thick silicon layers, respectively. The penalty of silica absorption is a propagation loss of approximately 6 dB/cm and 4 dB/cm for 220 nm and 300 nm thick silicon layers, respectively. The propagation loss can be further reduced using thicker silicon layers. Fortunately, the scattering loss decreases as the wavelength increases. Therefore, such a mature technology could still play a role in mid-infrared applications.