Electrospinning was used to fabricate bioactive nanofibrous membranes from cellulose nanocrystal-ZnO (CNC-ZnO) nanohybrids as reinforcing materials in biodegradable poly(3-hydroxybutyrate-co-3-hydroxy-valerate) (PHBV) for potential use as wound dressings. Incorporation of CNC-ZnO considerably improved the uniformity and reduced the diameter of PHBV nanofibers with porosity in the range of 14-56%. Significant improvements in mechanical strength and thermal stability were achieved. Compared to neat PHBV, a 150% improvement in tensile strength and a 112.5% increase in Young's modulus were obtained for the nanofibrous membranes with 5.0 wt% CNC-ZnO. Additionally, initial decomposition temperature (T (0)) and maximum decomposition temperature (T (max)) values were increased by 33.7 and 27.3 A degrees C, respectively. It was also observed that CNC-ZnO had a positive effect on the barrier properties and absorbency of simulated fresh blood for nanofibrous membranes. Moreover, the nanofibrous membrane with 5.0 wt% had the highest absorbency (8.4 g/g) and exhibited the best antibacterial activity of about 100% against both E. coli and S. aureus bacteria. Hence, such nanofibrous membranes showed potential uses as antibacterial wound dressings.