ABSTRACT Objective Increased risk of occupational exposure to bioaerosols has long been recognized in livestock operations including dairy facilities. Spanning the inhalable fraction (0–100 μm), dairy bioaerosols comprise a wide variety of inflammatory components that deposit in the nasopharyngeal region. The resultant inflammatory response from bioaerosol exposure is likely driving the increased prevalence of respiratory disease observed in dairy workers. It is also thought the microbiome of the upper respiratory system may help mediate this inflammation. We investigated the viability of a low-cost hypertonic saline nasal rinse intervention in modulating inflammatory responses in bioaerosol exposed dairy workers and its impact on microbial diversity. Methods Pre- and post-shift nasal rinses were administered and collected alongside full shift inhalable personal breathing zone (PBZ) samples for each participant for up to 5 consecutive days. Treatment group participants (n = 23) received hypertonic saline rinses while control group participants (n = 22) received normotonic saline rinses. Particulate matter (PM) and endotoxin concentrations were quantified from PBZ samples using gravimetric and enzymatic analytical methods, respectively. Pre- and post-shift rinses were analyzed for pro- and anti-inflammatory markers and microbial diversity using a multiplex assay and 16S rRNA sequencing, respectively. Results PM and endotoxin concentrations were comparable between groups indicating similar exposures. Post-shift pro-inflammatory markers were significantly higher than pre-shift for IL-13 (p = .047), IL-1β (p < .001), IL-6 (p < .001), IL-8 (p < .001), and TNF-α (p = .024). There was no evidence of a difference in log concentrations between intervention group or day among any of the measured inflammatory markers. Anti-inflammatory IL-10 concentrations increased across the 5 sample days, independent of treatment group suggesting tonicity may not be driving the change. However, this result was not significant (p = .217). Nasal microbiome alpha (within sample) and beta (between sample) diversity metrics did not differ significantly between group or day demonstrating no adverse washout intervention effects. Conclusion This study provided encouraging results that warrant future research to further evaluate saline nasal rinses as a workplace intervention.