Anthropogenic activities such as agriculture and industry increase contaminants that reach the water bodies, potentially threatening the biota. Most likely, these pollutants occur in complex mixtures. The effects on organisms can be potentiated (synergism) or reduced (antagonism) according to the interaction between the stressors or the species. Cadmium (Cd) is a toxic metal present in phosphate fertilizers, and fipronil is an insecticide broadly used in sugarcane crops. Copepods are important energy transfer links in aquatic environments, and effects on this group impact the whole trophic chain. In this study, we evaluated the responses of the freshwater Calanoida copepod Notodiaptomus iheringi, naturally present in water bodies that can be affected by sugarcane cultures in Brazil. The organisms were exposed to environmental concentrations of Cd and fipronil, isolated and in the mixture, in acute (48 h) and sub-chronic (8 d) tests. Our data indicate that both contaminants affect the survival of the organisms in acute or sub-chronic exposures. Cadmium did not affect egg production or hatching, while fipronil impacted these endpoints negatively. The Cd-fipronil combination resulted in antagonistic responses in survival (acute and sub-chronic) and egg production. A synergistic response was observed in egg hatching. Our results suggest that Cd presents a protective effect in the mixture with fipronil; however, it is not enough to prevent egg-hatching inhibition. These responses highlight how tricky it is to deal with pollutants’ interaction in environmental concentrations since synergism is the most common response to metal-pesticide mixtures. Our data point out N. iheringi as a sensitive organism in the presence of contaminants and reflects the threat of chemical mixtures in concentrations found in water bodies close to sugarcane crops in Brazil.