A key uncertainty for predicting future ocean oxygen levels is the response and feedback of organic matter respiration demand. One poorly understood component of the biological oxygen demand is the carbon-to-oxygen remineralization ratio – also called the respiration quotient. Currently, multiple biological hypotheses exist to explain variations in the respiration quotient of organic carbon produced in the surface ocean. To test these hypotheses, we here directly quantified the particulate respiration quotient in 715 samples along a meridional section of the Atlantic Ocean and compared to previous observations from the Pacific Ocean. We demonstrate significant regional shifts in the respiration quotient and a two-basin average of 1.16. Diel oscillations were observed in the respiration quotient. Basin and regional variation were linked to temperature, N vs. P stress and shifts in plankton size structure. These observations suggest a complex regulation of the respiration quotient with important implications for the regional coupling of carbon and oxygen cycling.