As a potential remedy for COVID-19 treatment, hydroxychloroquine (HCQ) attracted considerable scholarly attention early in the pandemic. However, the ecological consequences of HCQ are not well understood, especially regarding their interactions with plastic waste such as nano-and microplastics (PS). This study aimed to investigate colloidal stability, bioaccumulation, and acute toxicity of carboxylate-modified polystyrene-based PS and HCQ, both alone and in combination, to Salmo trutta embryos and larvae. Spectroscopic properties of PS were found to change over time and to be affected by the presence of HCQ in the incubation water of organisms. Confocal microscopy showed that PS and HCQ, both alone and in combination, caused damage to the chorion of the exposed fish embryos. Particles of PS were detected in external tissues of larvae. The impact of the tested substances on fish was found to be dependent on the PS particle size, exposure duration, and the life stage of fish.