The existing and rising anti-Semitism is a risk factor for the mental health of Jewish people worldwide. This study examines possible associations between anti-Semitism and mental health in offspring/children (OHS) and grandchildren (GHS) of Holocaust survivors through cross-country comparisons. A total of n = 248 OHS and n = 240 GHS from Israel, Germany, and the US completed a cross-sectional online survey on experiences of anti-Semitism, psychological distress, and posttraumatic stress symptoms, offered in English, German, and Hebrew. Psychological distress was significantly higher among participants from Germany vs. Israel and the US. Significant differences in experiences of anti-Semitism were found between the generations, with higher rates in GHS. Experiences of anti-Semitism were found to be associated with a higher risk for psychological distress and probable posttraumatic stress disorder (PTSD). The study emphasises the severe psychological stress being associated with experiences of anti-Semitism among OHS and GHS across different countries of origin. Given the rise in anti-Semitism since October 7, 2023 onwards, the findings are a warning and a clear impetus for political authorities as well as civil society to strengthen efforts for better healthcare and protecting Jewish life worldwide.