TEMPO nanofibrillated cellulose (TNFC) from two underutilized Appalachian hardwoods, Northern red oak (Quercus rubra) and yellow poplar (Liriodendron tulipifera), was prepared to determine its feasibility to be used as template for antimicrobial metallic copper particles. In addition, a comparison of the TNFC from the two species in terms of their morphological, chemical, thermal, and mechanical properties was also performed. The woody biomass was provided in the form of logging residue from Preston County, West Virginia. A traditional kraft process was used to produce the pulp followed by a five-stage bleaching. Bleached pulps were then subjected to a TEMPO oxidation process using the TEMPO/NaBr/NaClO system to facilitate the final mechanical fibrillation process and surface incorporation of metallic copper. The final TNFC diameters for red oak and yellow poplar presented similar dimensions, 3.8 ± 0.74 nm and 3.6 ± 0.85 nm, respectively. The TNFC films fabricated from both species exhibited no statistical differences in both Young's modulus and the final strength properties. Likely, after the TEMPO oxidation process both species exhibited similar carboxyl group content, of approximately 0.8 mmol/g, and both species demonstrated excellent capability to incorporate antimicrobial copper on their surfaces.