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How the remote influences of El Niño-Southern Oscillation (ENSO) may vary in a warmer future remains a hot topic but still elusive. Based on the outputs from the Paleoclimate Modeling Intercomparison Project Phase 4, here we investigated the variations of ENSO teleconnections in boreal winter during the Last Interglacial (LIG), which shares large similarities with the projected climatic features in the 21st century. Our results suggested that the ENSO-temperature teleconnections on average weakened by ∼13.4% during the LIG relative to the preindustrial, whereas the response of precipitation amplified by ∼5.0%. However, there are large regional discrepancies in the variations of ENSO teleconnections in terms of the sign and amplitude. For example, we observed significant ENSO-temperature relationship changes at the high latitudes during the LIG, with a depressed linkage over northern North America but enhanced linkage over the high latitudes of Eurasia. The most profound change in ENSO-precipitation teleconnection occurred over the tropics during the LIG, characterized by a weaker response over the equatorial Pacific Ocean whereas a stronger response over the Maritime Continent and adjacent oceans. Regarding atmospheric circulations, we found that the ENSO-driven Walker Circulations over the Pacific and the Indian Ocean shifted westward during the LIG, whereas the descending branch of the ENSO-driven Atlantic Walker Circulation shifted eastward. Our results provide a model-based scenario for the variations of ENSO teleconnections during the LIG, but the underlying mechanisms deserve further investigation in the future. • ENSO-temperature teleconnections on average weakened during the Last Interglacial. • ENSO-precipitation teleconnections on average enhanced during the Last Interglacial. • There are large regional discrepancies in the variations of ENSO teleconnections. • ENSO-driven Pacific Walker Circulation moved westward during the Last Interglacial. [ABSTRACT FROM AUTHOR]