This study evaluated the size-dependent effects of high-density polyethylene (HDPE) fragments in zebrafish. Larvae were exposed to HDPE microplastic (MP) in three sizes, small (14.12 μm), medium (80.32 μm), and large (120.97 μm), at 20 mg/L. Size-dependent effects in terms of MP intake, subsequent gut damage, and behavioral changes were observed. The results showed that HDPE exposure did not affect the survivability of zebrafish larvae but caused two significant changes. First, exposure to large MPs caused the most serious damage to hair cells and mechanosensory receptors in the fish's lateral line system. Second, exposure to MPs < 100 μm resulted in their ingestion by larvae, thereby causing morphological changes in the gastrointestinal tract. All larvae exposed to MPs showed behavioral pattern changes associated with size differences. This study improves our understanding of the effects of MPs on aquatic organisms and highlights the need to implement efficient strategies for plastic waste management.