Due to the shortage of masks during the pandemic, we recently demonstrated that household textiles are effective environmental droplet barriers (EDBs) with identical droplet retention potential as medical masks. To further promote the implementation of a universal community droplet reduction solution based on a synchronized encouragement/enforcement of mask utilization by the public based on widely available textiles (mask fabrication without the need for sewing machines), here we conducted a study using germ-free mice to determine to what extent textiles were effective in vivo. Using a bacterial-suspension spray simulation model of droplet ejection (mimicking a sneeze), we quantified the extent by which 100% cotton textile prevented the contamination of germ-free animals on the other side of the textile-barrier (simulating a properly worn mask). Of relevance, all mice protected with textiles remained germ-free after two sprays (inoculation dose: >600 bacterial droplet units per 56.75cm2) compared to the contamination of mice not protected by a textile (0/12 vs 6/6, Fisher’s exact, p<0.0001). In a second phase of the experiment with 12 germ-free mice exposed again to 10-fold more droplets remained germ-free, while 100% of mice at 180cm became colonized with a single spray (0/8 vs 4/4, Fisher exact, p=0.002). Collectively, barriers protected all mice (even with low-density textiles, heavy vs. light fabric, T-test, p=0.0028) when using textile-EDB to cover the cages (0/20 vs 10/10, Fisher exact, p<0.0001). This study demonstrated, in vivo, that widely available household textiles are 100% effective at preventing contamination of the environment and the exposed animals by microbe-carrying droplets.