The El Cañizar de Villarquemado pollen record covers the last part of MIS 6 to the Late Holocene. We use Tolerance-Weighted Averaging Partial Least Squares (TWA-PLS) to reconstruct mean temperature of the coldest month (MTCO) and growing degree days above 0°C (GDD0) and the ratio of annual precipitation to annual potential evapotranspiration (MI), accounting for the ecophysiological effect of changing CO2 on water-use efficiency. Rapid summer warming occurred during the Zeifen-Kattegat Oscillation at the transition to MIS 5. Summers were cold during MIS 4 and MIS 2, but some intervals of MIS 3 had summers as warm as the warmest phases of MIS 5 or the Holocene. Winter temperatures declined from MIS 4 to MIS 2. Changes in temperature seasonality within MIS 5 and MIS 1 are consistent with insolation seasonality changes. Conditions became progressively more humid during MIS 5, and MIS 4 was also humid, although MIS 3 was more arid. Changes in MI and GDD0 are anti-correlated, with increased MI during summer warming intervals. Comparison with other records shows glacial-interglacial changes were not unform across the circum-Mediterranean region, but available quantitative reconstructions are insufficient to determine if east-west differences reflect the circulation-driven precipitation dipole seen in recent decades.