Thawing permafrost and the resulting mineralization of previously frozen organic carbon (C) is considered an important future feedback from terrestrial ecosystems to the atmosphere. Here, we use a dynamic process oriented permafrost model, the CoupModel, to link surface and subsurface temperatures from a moist permafrost soil in High-Arctic Greenland with observed heat production and carbon dioxide (CO2) release rates from decomposition of previously frozen organic matter. Observations show that the maximum thickness of the active layer at the end of the summer has increased 1 cm yr−1 since 1996. The model is successfully adjusted and applied for the study area and shown to be able to simulate active layer dynamics. Subsequently, the model is used to predict the active layer thickness under future warming scenarios. The model predicts an increase of maximum active layer thickness from today 70 to 80–105 cm as a result of a 2–6 °C warming. An additional increase in the maximum active layer thickness of a few centimetres may be expected due to heat production from decomposition of organic matter. Simulated future soil temperatures and water contents are subsequently used with measured basal soil respiration rates in a respiration model to predict the corresponding depth-integrated CO2 production from permafrost layers between 0.7 and 2 m below the surface. Results show an increase from present values of <40 g C m−2 yr−1 to between 120 and 213 g C m−2 yr−1 depending on the magnitude of predicted warming. These rates are more than 50% of the present soil CO2 efflux measured at the soil surface. Future modelling accounting for snow, vegetation and internal biological heat feedbacks are of interest in order to test the robustness of the above predictions and to describe the entire ecosystem response.