Molecular gene cycling is useful for determining body-time-of-day (BTOD) with important applications in personalized medicine including cardiovascular disease and cancer, our leading causes of death. However, it impractically requires repetitive invasive tissue sampling that is obviously not applicable for humans. Here we characterize diurnal protein cycling in blood using high-throughput proteomics; blood proteins are easily accessible, minimally invasive, and importantly can serve as surrogates for what is happening elsewhere in the body in health and disease. As proof of concept, we used normal C57BL/6 mice maintained under regular 24h light and dark cycles. First we demonstrate fingerprint patterns in 24h plasma, revealed using surface enhanced laser desorption and ionization (SELDI). Second, we characterize diurnal cycling proteins in blood using chromatography and tandem electrospray ionization mass spectrometry (MS). Importantly, we note little association between the cycling blood proteome and tissue transcriptome, delineating the necessity to identify de novo cycling proteins in blood for measuring BTOD. Furthermore, we explore known interaction networks to identify putative functional pathways regulating protein expression patterns in blood, thus shedding new light on our understanding of integrative physiology. These studies have profound clinical significance in translating the concept of BTOD to the practical realm for molecular diagnostics, and open new opportunities for clinically relevant discoveries when applied to ELISA-based molecular testing and/or point-of-care devices.