Display omitted •DOM decreased bioaccumulation of ERY in aquatic organisms.•SRHA and SRFA inhibited ERY bioavailability greater than the other DOM.•ERY KDOC values increased with the content of humic and fulvic acid-like compounds.•DOM interacted with ERY via reactions of −COO− with ERY+ and H-bonding.•Inhibitory effects of DOM were related with its sources and properties. Macrolides are widely used antibiotics with ubiquitous occurrence in aquatic environments. Unlike many emerging contaminants, macrolides are positively charged on their amine groups and are likely to interact with negative charge groups of dissolved organic matters (DOMs), which may alter macrolide bioaccumulation but yet to be explored. Here we evaluated the effects of different DOM (LeHA, PPHA, SRHA and SRFA) on erythromycin (an important macrolide) bioaccumulation into aquatic biota with 14C tracing. Results showed that ERY uptake in organisms was significantly inhibited by DOM (P < 0.05). In the presence of DOM at 20 mg L−1, the averaged equilibrium concentration (Ce) decreased by 28.1–40.6% for zebrafish and 10.9–25.8% for duckweed, corresponding to reductions in the bioconcentration factor (BCF) by 15.9–32.8% and 10.9–18.5%, respectively. Likely due to their higher carboxyl group content, SRHA and SRFA exhibited stronger inhibitory effects than LeHA or PPHA. The possible interactions between ERY and DOM were explored and results suggested that DOM inhibited ERY bioavailability by forming DOM-ERY complexes via ionic bonding of −COO− and ERY+, hydrogen bonding and hydrophobic partitioning. This study was the first to report on inhibitory effects of DOM on erythromycin bioavailability and has important implications for better understanding risks of macrolides.