Applications based on silicene as grown on substrates are of high interest toward actual utilization of this unique material. Here we explore, from first principles, the nature of carbon monoxide adsorption on semiconducting silicene nanoribbons and the resulting quantum conduction modulation with and without silver contacts for sensing applications. We find that quantum conduction is detectably modified by weak chemisorption of a single CO molecule on a pristine silicene nanoribbon. This modification can be attributed to the charge transfer from CO to the silicene nanoribbon and the deformation induced by the CO chemisorption. Moderate binding energies provide an optimal mix of high detectability and recoverability. With Ag contacts attached to a ~1 nm silicene nanoribbon, the interface states mask the conductance modulations caused by CO adsorption, emphasizing length effects for sensor applications. The effects of atmospheric gases—nitrogen, oxygen, carbon dioxide, and water—as well as CO adsorption density and edge-dangling bond defects, on sensor functionality are also investigated. Our results reveal pristine silicene nanoribbons as a promising new sensing material with single molecule resolution.