Wastewater may alter riverine fluxes of dissolved organic matter (DOM) and CO2, yet little is known about how treated and untreated wastewater affects riverine DOM biodegradation and CO2 emission to a different degree. In order to compare effects of treated vs untreated wastewater on DOM biodegradation and CO2 emission in downstream rivers, a three-day incubation experiment with river water mixed with wastewater (10%) was conducted under dark laboratory conditions. Initial dissolved organic carbon (DOC) concentrations were eight times higher in untreated sewage from Phnom Penh than in effluents from a wastewater treatment plant. Biodegradable DOC (BDOC) measured as % of initial DOC during the three-day incubation was 31 times higher in sewage than in treated wastewater, indicating abundant labile DOM moieties in sewage. The mixtures showed higher concentrations of BDOC and dissolved CO2 than the levels expected from the mixing ratio, suggesting mixing-enhanced biodegradation of DOM. Differential excitation-emission matrices (EEMs) exhibited consistent patterns of enhanced consumption of DOM especially in untreated wastewater and its mixtures. Overall results suggest that labile DOM derived from sewage can enhance the biodegradation of riverine DOM and hence CO2 emission, especially in rapidly urbanizing river systems receiving loads of untreated sewage across developing countries.