Abstract The search for signs of life beyond Earth is a crucial driving motivation of exoplanet science, fueling new work on biosignature gases in habitable exoplanet atmospheres. We study carbonyls, a category of molecules containing the C=O double bond, following our proposal to systematically identify plausible biosignature gas candidates from a list of all small volatile molecules. We rule out carbonyls as biosignature gases due to both their high water solubility and their high photolysis rate, despite their ubiquitous production by life on Earth, their critical importance in Earth’s life biochemistry, and their uniquely identifiable molecular spectral features in mid- to low-resolution spectroscopy. Even in scenarios where life is a large net source of carbonyls, we demonstrate that detection of carbonyls is not possible on even the most ideal habitable exoplanet, because only 10 ppb of carbonyls can accumulate under our most optimistic assumptions. Moreover, high biological fluxes of organic carbon gases, while mathematically possible, are likely biologically unattainable due to the resulting huge waste of carbon—a main building block for life. Our simulations show that photochemical processing of carbonyls leads to generation of CO in quantities that can reengineer the atmosphere, affirming the ambiguity of CO as an antibiosignature. Overall, we find that the expression of a carbonyl-producing biosphere by CO, though potentially detectable by the James Webb Space Telescope, is unable to be uniquely traced back to carbonyls. While carbonyls fail as a bioindicator, by investigating them we have made a significant step toward systematically assessing the biosignature gas potential of all small volatile molecules.