Feeding colostrum to calves within 24 h after birth is vital for passive transfer of immunity. Within the US dairy industry, decisions made in colostrum management programs have increasingly hinged upon the idea of colostrum being of “good quality” or “poor quality.” In the United States, the Brix refractometer, designed to measure sugars in solution, has been widely adapted as an on-farm tool to measure colostrum IgG concentration, with a score below ~22% Brix (50 g/L IgG) generally considered not acceptable for heifer calves. As such, current colostrum management decisions might benefit from application of knowledge of mammary gland physiology. The objective of this study was to (1) determine the relationship between volume produced, Brix, total protein, IgG in colostrum, and to investigate the influence of lipids on Brix scores, and (2) use such relationships to suggest a more physiology-based colostrum management program. In this study, colostrum samples were obtained from primiparous and multiparous Holstein cows of varying ages at +1, +4, +12, +20, and +28 h post-parturition. Volume produced for the first milking varied for n = 32 primiparous cow (5.5 ± 2.79 L) and n= 67 multiparous cows (6.33 ± 4.42 L). Brix values were determined by an optical refractometer and found to average 22.25 ± 1.26 Brix for primiparous and 25.1 ± 5.74 Brix for multiparous cows. Average total protein content (measured by BCA) also varied amongst samples (n=5) and did not significantly change after fat removal by centrifugation (−2.43 µg/µL ± 23.97 µg/µL). We used quantitative fluorescent Western blot analysis to measure kinetics of IgG levels in colostrum post-parturition, to emulate physiological availability to a suckling calf. Based on the variability in colostrum volume produced per cow and milking, our findings suggest that adjusting volume of colostrum fed to calves based on IgG concentration to reach a threshold IgG delivery would best mimic the natural transfer of passive immunity. This physiology-based colostrum management would likely aid in improving calf health and growth by ensuring optimum IgG supply.