Variability and long-term climate change in the Baltic Sea region is investigated for the pre-industrial period of the last millennium. For the first time dynamical downscaling covering the complete millennium is conducted with a regional climate model in this area. As a result of changing external forcing conditions, the model simulation shows warm conditions in the first centuries followed by a gradual cooling until ca. 1700 before temperature increases in the last centuries. This long-term evolution, with a Medieval Climate Anomaly (MCA) and a Little Ice Age (LIA), is in broad agreement with proxy-based reconstructions. However, the timing of warm and cold events is not captured at all times. We show that the regional response to the global climate anomalies is to a strong degree modified by the large-scale circulation in the model. In particular, we find that a positive phase of the North Atlantic Oscillation (NAO) simulated during MCA contributes to enhancing winter temperatures and precipitation in the region while a negative NAO index in the LIA reduces them. In a second step, the regional ocean model (RCO-SCOBI) is used to investigate the impact of atmospheric changes onto the Baltic Sea for two 100 yr time slices representing the MCA and the LIA. Besides the warming of the Baltic Sea, the water becomes fresher at all levels during the MCA. This is induced by increased runoff and stronger westerly winds. Moreover, the oxygen concentrations in the deep layers are slightly reduced during the MCA. Additional sensitivity studies are conducted to investigate the impact of even higher temperatures and increased nutrient loads. The presented experiments suggest that changing nutrient loads may be more important determining oxygen depletion than changes in temperature or dynamic feedbacks.