This study investigated the short‑term effects of polyethylene microplastics (PE‑MPs) on the marine mussel Mytilus edulis using a suite of cellular and subcellular biomarkers. A total of 225 mussels were collected from Umluj, Saudi Arabia, a relatively unimpacted coastal area of the Red Sea, and experimentally exposed for 72 h to spherical PE‑MPs (50 μm diameter) at nominal concentrations of 5, 10, 20, and 60 particles L-1. Genotoxicity, oxidative status, and cellular integrity were assessed by comet assay, thiobarbituric acid‑reactive substances (TBARS), superoxide dismutase (SOD) activity, and lysosomal membrane stability (LMS). At 60 particles L-1, DNA strand breakage increased markedly in hemocytes (13.09%) and gill cells (12.21%) relative to controls (2.14%; p < 0.01). Lipid peroxidation was 1.28 nmol TBARS mg protein-1, and activity of gill SOD was decreased by 16.13% of control. LMS was significantly reduced from 134.4 min in controls to 53.2 min in the highest exposure (p < 0.01), suggesting impaired cellular homeostasis. Given the short exposure duration, these results are preliminary. They indicate that acute PE-MP exposure at the tested concentrations is associated with measurable genotoxicity, oxidative stress, and reduced lysosomal stability. Longer-term ecological implications remain to be investigated.