Cortical remodeling is a process that replaces primary bone tissue with secondary or osteonal bone. Osteonal bone is characterized by the presence of secondary osteons or Haversian systems, which are cylindrical structures made up of concentric layers of bone tissue known as lamellae that surround a central canal. Remodeling is mediated by specialized cells known as osteoclasts and osteoblasts. These cells are signaled to selectively resorb and deposit secondary bone in specific areas by mechanical strain. Variations in the loading environment of bones can produce variations in secondary osteon size and morphology. This study investigated the effect of diverse in vivo loading (compression vs. tension) on the morphology of secondary osteons in the cranial (subjected to tensile loading) and caudal (subjected to compressive loading) aspects of the proximal humerus of white-tailed deer. Next, bone samples from the cranial and caudal aspects were mechanically tested in compression to find the stiffness of secondary osteonal bone in the proximal humerus of white-tailed deer. Finally, the bone samples were ashed and their composition was recorded (mineral, organic material and water content). Our histological results revealed significantly larger and more medially oriented secondary osteons with relatively smaller central canals in the cranial region. Nevertheless, Young’s moduli and ash content were not significantly different between the cranial and caudal regions in all three principle axes (axial, radial and transverse). These results indicate that during bone remodeling - osteoclasts (bone resorbing cells) but not osteoblasts (bone depositing cells) are affected by the in vivo type and magnitude of loading. While the type of physiological stress affects bone resorption by osteoclasts (smaller cutting cones and consequently smaller secondary osteons under compression), bone deposition and mineralization by osteoblasts doesn’t differ. Consequently, cortical bone compressive stiffness is not affected by the type of physiological stresses.