Suspended particles (SP) exist widely in various water systems and are able to adsorb other pollutants in water, producing ecotoxic effects on aquatic nontarget species. Until now, however, few studies have focused on the effects of SP on antibiotics. Therefore, the present study investigated the effects of the mixtures of SP and phenicol antibiotics (chloramphenicol [CAP], thiamphenicol [TAP]) on acute toxicity and oxidative stress responses in Daphnia magna. The results indicated that the acute toxicity of phenicol antibiotics in D. magna was increased when combined with SP. Besides, the immobilization of daphnids caused by phenicol drugs in the presence of 10 mg/L of SP was more intense than that with 200 mg/L of SP. Furthermore, the impact of SP with diverse concentrations on the activity of catalase and the level of reduced glutathione in D. magna was different. Notably, almost all CAP + TAP + SP treatments markedly increased malondialdehyde content in D. magna, causing potential cellular oxidative damage in D. magna. In summary, the present study provides insights into the toxic effects of phenicol antibiotic and SP mixtures on aquatic organisms. Environ Toxicol Chem 2021;40:2463–2473. © 2021 SETAC