In this work, we designed an anti-microbial scaffold using polycaprolactone (PCL) polymer blended with silver sulfadiazine (AgSD). This scaffold was prepared by an electrospinning (ELSP) method. The fabricated PCL and AgSD embedded within the PCL fibers were prepared and subsequently characterized using field emission scanning electron microscopy (FE-SEM) with image mapping and thermogravimetric analysis (TGA). In vitro antimicrobial activity of the PCL-AgSD nanofibers was evaluated against Staphylococcus aureus, methicillin-resistant S. aureus, and S. epidermidis. The PCL-AgSD fibers exhibited higher antimicrobial activity against all the tested organisms as compared to control PCL fibers. This design of PCL-AgSD nanofibers holds promise for a wide variety of bio-tissue and bioengineering applications.