Oxygen depletion in confined spaces represents one of the most serious and underestimated dangers for workers. Despite the existence of several commercially available and widely used gas oxygen sensors, injuries and deaths from reduced oxygen levels are still more common than for other hazardous gases. Here, we present hydrogel-based organic electrochemical transistors (OECTs) made with the conducting polymer poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS) as wearable and real-time oxygen gas sensors. After comparing OECT performances using liquid and hydrogel electrolytes, we identified the best PEDOT:PSS active layer and hydrogel coating (30 µm) combination for sensing oxygen in the concentration range of 13–21% (v/v), critical for work safety applications. The fast O2 solubilization in the hydrogel allowed for gaseous oxygen transduction in an electrical signal thanks to the electrocatalytic activity of PEDOT:PSS, while OECT architecture amplified the response (gain ~ 104). OECTs proved to have comparable sensitivities if fabricated on glass and thin plastic substrates, (−12.2 ± 0.6) and (−15.4 ± 0.4) µA/dec, respectively, with low power consumption (<40 µW). Sample bending does not influence the device response, demonstrating that our real-time conformable and lightweight sensor could be implemented as a wearable, noninvasive safety tool for operators working in potentially hazardous confined spaces.