Proxy-data suggest that the Last Interglacial (LIG; ~130-116 ka BP) climate was characterized by higher temperatures, a partially melted Greenland Ice Sheet (GIS) and a changed Atlantic meridional overturning circulation (AMOC). Notwithstanding the uncertainties in LIG palaeoclimatic reconstructions, this setting potentially provides an opportunity to evaluate the relation between GIS melt and the AMOC as simulated by climate models. However, first we need to assess the extent to which a causal relation between early LIG GIS melt and the weakened AMOC is plausible. With a series of transient LIG climate simulations with the LOVECLIM earth system model, we quantify the importance of the major known uncertainties involved in early LIG GIS melt scenarios. Based on this we construct a specific scenario that is within the parameter space of uncertainties and show that it is physically consistent that early LIG GIS melting kept the AMOC weakened. Notwithstanding, this scenario is at the extreme end of the parameter space. Assuming that proxy-based reconstructions of early LIG AMOC weakening offer a realistic representation of its past state, this indicates that either (1) the AMOC weakening was caused by other forcings than early LIG GIS melt or (2) the early LIG AMOC was less stable than indicated by our simulations and a small amount of GIS melt was sufficient to keep the AMOC in the weak state of a bi-stable regime. We argue that more intensive research is required because of the high potential of the early LIG to evaluate model performance in relation to the AMOC response to GIS melt. © 2013 Springer-Verlag Berlin Heidelberg.