Early postnatal life involves rapid physiological and immunological adaptation as the newborn transitions from intrauterine to extrauterine conditions. These processes are reflected in the circulating plasma proteome and affect key blood functions, including homeostasis, hemostasis, and immune defense. During pregnancy, immune tolerance is tightly regulated within the largely sterile intrauterine environment. After birth, the neonatal immune system undergoes rapid maturation to balance antimicrobial defense with colonization by commensal microbes. This early-life immune development, primarily driven by innate immune mechanisms and maternally derived antibodies, has long-term implications for health and disease and exhibits sex-specific characteristics. To characterize early plasma proteome dynamics, this study leverages a large, well-controlled cohort of 679 healthy term newborns enrolled in The Gambia as part of the NIH/NIAID Human Immunology Project Consortium (HIPC). Peripheral blood samples were obtained from all participants within the first 24 hours of life (Day of Life 0), with additional samples collected from a subset on Day of Life 1, resulting in 906 plasma samples spanning the first 48 hours after birth. Using a high-throughput targeted mass spectrometry approach, plasma proteins were quantified at bi-hourly resolution. The dataset provides a normative, high-resolution resource for studying early-life proteome dynamics and supports future mechanistic and functional investigations in human neonatal biology.