Metabolism is vital for brain function. The nervous system’s vulnerability to energy metabolism disruptions stems from its unyielding and substantial energy requirements. Understanding the mammalian brain’s metabolic dynamics offers valuable insights into the intricate relationship between metabolism and higher cognitive functions. A systematic and high-throughput investigation to understand the metabolic exchange between the human brain and circulatory system has, however, been lacking. We compared metabolomes and lipidomes of blood samples from the cerebral venous sinus and femoral artery to profile the brain’s uptake and release of metabolites and lipids. Our data also showed age-related alterations in the uptake and release of metabolites. These results provide a comprehensive view of metabolic consumption and production processes within the human brain.