Humans have drastically altered the transport and composition of material subsidies between terrestrial and aquatic ecosystems. In lakes, eutrophication and brownification have resulted from increased concentrations of two dominant chemical regulators: phosphorus and coloured dissolved organic matter (CDOM). However, the mechanisms underlying the interactive effect of these drivers on lake ecosystem functioning are not well understood because phosphorus and CDOM inputs to lakes are often concomitant, and emergent patterns may be the result of both direct physiological responses and indirect effects mediated by trophic interactions. We used manipulations in 21 large (1270 m3) lake enclosures in Germany (www.lake-lab.de) to disentangle how phosphorus and CDOM inputs affect whole ecosystem metabolism. Daily rates of gross primary production (GPP) and ecosystem respiration (ER) were modelled from high-frequency measurements of dissolved oxygen concentration for six weeks following one pulsed addition of three levels of CDOM across a seven-step gradient of total phosphorus. Phosphorus and CDOM and addition had an interactive effect on autotrophic processes in the upper mixed layer; nutrients stimulated GPP only in the absence of light limitation that was induced by CDOM. ER showed a similar response, driven by a tight coupling to labile organic matter production by autotrophs in all treatments. However, there was also a small increase in the respiration of organic matter that was not coupled to GPP in enclosures with higher concentrations of CDOM. This effect partly offset the reduction in ER that was associated with lower GPP in darkened enclosures, producing an overall decrease in net ecosystem productivity (i.e. GPP – ER). Our results demonstrate that multiple drivers affect carbon cycling in lakes via a complex suite of physicochemical and biological mechanisms with implications for patterns of energy flow through the pelagic food web.