The long-term warmth of the Eocene (~56 to 34 million years ago) is commonly associated with elevated partial pressure of atmospheric carbon dioxide (pCO(2)). However, a direct relationship between the two has not been established for short-term climate perturbations. We reconstructed changes in both pCO(2) and temperature over an episode of transient global warming called the Middle Eocene Climatic Optimum (MECO; ~40 million years ago). Organic molecular paleothermometry indicates a warming of southwest Pacific sea surface temperatures (SSTs) by 3° to 6°C. Reconstructions of pCO(2) indicate a concomitant increase by a factor of 2 to 3. The marked consistency between SST and pCO(2) trends during the MECO suggests that elevated pCO(2) played a major role in global warming during the MECO.