The Cretaceous Period (145-66 Ma) provides an opportunity to obtain insights into the adaptation of the climate system to increased atmospheric greenhouse gas concentrations. The organic paleothermometer TEX86 is one of the few proxies available for reconstructing quantitative estimates of upper ocean temperatures of this time period. Here we show that the sedimentary TEX86 signal in the Early Cretaceous North and South Atlantic shows systematic differences to other Cretaceous samples. In particular, the relative increase in the fractional abundances of the crenarchaeol isomer compared to crenarchaeol exhibits similarities with surface sediments from the modern Mediterranean and Red Sea. Dedicated climate model simulations suggest that the formation of warm and saline deep waters in the restricted North and South Atlantic may have influenced TEX86 export dynamics leading to a warm bias in reconstructed upper ocean temperatures. Applying a regional calibration from the modern Mediterranean and Red Sea to corresponding TEX86 data significantly improves the model-data fit for the Aptian Oceanic Anoxic Event 1a and the overall comparison with other temperature proxies for the Early Cretaceous. Our results demonstrate the need to consider regional and temporal changes of the TEX86-temperature relation for the reconstruction of deep-time ocean temperatures.