BACKGROUND AND AIMS: Hepatitis E virus (HEV), similar to hepatitis A virus (HAV), has been linked to cases associated with mussel consumption, and several studies have detected HEV in commercially available mussels. While extensive data exists on HEV contamination in mussels from tropical regions, the Mediterranean Sea, and the North Sea, there is a lack of information regarding the potential risk posed by common mussels (Mytilidae) from the Baltic Sea. Furthermore, no experimental studies have investigated the ability of Baltic Sea mussels to be infected with HEV. MATERIAL AND METHODS: Healthcare workers (n = 447) from the University Medical Center Hamburg Eppendorf, Germany, were surveyed regarding their mussel consumption habits and tested for anti-HEV IgG using a commercially available assay. Commercially sourced Baltic Sea Mytilidae, obtained from local retailers, were tested for HEV using a validated PCR method. Additionally, 50 live Mytilidae were experimentally spiked with HEV, followed by dissection and separate PCR analysis of the gastrointestinal tract, gonads, and muscle tissue. RESULTS: There was no significant difference in the likelihood of anti-HEV IgG positivity between individuals who frequently consumed mussels and those who did not. None of the 40 commercial mussel samples tested were positive for HEV. HEV RNA was detected in the gastrointestinal tract of experimentally exposed Mytilidae specimen but not in their gonads or muscle tissue. It was observed that HEV RNA persisted in the gastrointestinal tract for more than 14 days but not beyond 21 days. DISCUSSION: This study provides no evidence of HEV contamination in commercially sourced Baltic Sea mussels, as all tested samples were negative for HEV RNA. Moreover, no significant association was observed between mussel consumption and anti-HEV IgG positivity among healthcare workers. Experimental exposure revealed that HEV RNA can persist in the gastrointestinal tract of Baltic Sea mussels for over 16 days but less than 24 days, while no viral presence was detected in the gonad or muscle tissue. These findings suggest a minimal risk of HEV transmission through mussels from the Baltic Sea but highlight the need for further studies to understand their role in HEV ecology.