Several studies have measured the effectiveness of masks at retaining particles of various sizes
in vitro
. To identify a functional
in vivo
model, herein we used germ-free (GF) mice to test the effectiveness of textiles as filtration material and droplet barriers to complement available
in vitro
-based knowledge. Herein, we report a study conducted
in vivo
with bacteria-carrying microdroplets to determine to what extent household textiles prevent contamination of GF mice in their environment. Using a recently validated spray-simulation method (mimicking a sneeze), herein we first determined that combed-cotton textiles used as two-layer-barriers covering the mouse cages prevented the contamination of all GF animals when sprayed 10–20 bacterial-droplet units/cm
2
. In additional to exposure trials, the model showed that GF mice were again protected by the combed-cotton textile after the acute exposure to 10 times more droplets (20 “spray-sneezes”, ~200 bacterial-droplet units/cm
2
). Overall, two-layer combed-cotton protected 100% of the GF mice from bacteria-carrying droplets (
n
= 20 exposure-events), which was significantly superior compared to 100% mouse contamination without textile coverage or when 95% partly covered (
n
= 18, Fisher-exact,
p
< 0.0001). Of relevance is that two different densities of cotton were equally effective (100%) in preventing contamination regardless of density (120–vs. 200 g/m
2
;
T
-test,
p
= 0.0028), suggesting that similar density materials could prevent droplet contamination. As a practical message, we conducted a speech trial (counting numbers, 1–100) with/without the protection of the same cotton textile used as face cover. The trial illustrated that contamination of surfaces occurs at a rate of >2–6 bacteria-carrying saliva-droplets per word (2.6 droplets/cm
2
, 30 cm) when speaking at 60–70 decibels and that cotton face covers fully prevent bacterial surface contamination.