Selective serotonin reuptake inhibitors (SSRIs) are neurologically active drugs that can contaminate surface waters and have the potential to negatively affect aquatic organisms. In this investigation, the 48‐h acute toxicity of mixtures (binary and quaternary) of four common SSRIs (fluoxetine [Prozac®], sertraline [Zoloft®], paroxetine [Paxil®], and citalopram [Celexa®]) were determined in the daphnid Ceriodaphnia dubia. Logistic regression was used to model mortality data and to investigate the applicability of concentration addition and independent action models to explain observed mortality. The concentrations estimated to induce 50% mortality in 48 h for the individual SSRIs sertraline, fluoxetine, paroxetine, and citalopram were 0.48 to 0.66, 1.23 to 1.84, 2.23 to 3.57, and 10.47 to 14.53 μM, respectively. Concentration addition was a better predictor of mixture effects than independent action and suggested that the tested SSRIs have a similar mechanism of action. Results indicate that environmental hazard assessments should be conservative and consider that acutely toxic effects in aquatic organisms can be additive for each SSRI in a mixture.