Rationale: Respiratory failure from Acute Respiratory Distress Syndrome or ARDS is a leading cause of mortality in patients with respiratory infections. Early administration of dexamethasone has shown to reduce mortality in patients with moderate-to-severe ARDS associated to infectious diseases, such us COVID-19. Our aim was to compare IRL201104 with dexamethasone in a classical model of ARDS to explore its potential in the treatment of this patient population. Methods: Mice received IRL201104 (0.02ng/kg-20μg/kg i.v.), vehicle or dexamethasone (1mg/kg i.p.) before an aerosol challenge with bacterial lipopolysaccharide (LPS). 4hrs post-LPS bronchoalveolar lavage fluid (BALF) was collected and both cell infiltration and cytokine/chemokine levels were measured. Results: IRL201104 dose-dependently reduced LPS-induced neutrophilia with the top dose effect being comparable to that of dexamethasone. Treatment with IRL201104 also caused a significant and dose dependent reduction of proinflammatory cytokines/chemokines in BALF including TNF-α, IL-1β, IFN-γ, IL-6, IL-10, IL-17, KC/IL-8, G-CSF, GM-CSF, MCP-1, MIP-1a and MIP-3a. This effect was at least as good as steroid treatment. Conclusions: Strategies preventing the action of neutrophils/stopping the excessive lung infiltration of neutrophils may reduce the severity of the ARDS associated with respiratory infections and so provide the patient with a more favorable outcome. IRL201104 showed an effect on neutrophilic infiltration comparable to current standard of care dexamethasone, significantly impacting several proinflammatory cytokines and chemokines that has been associated with disease severity and progression such us IL-6, TNF-α, GM-CSF or MCP-1. Unlike steroids, IRL201104 shows a clean safety profile and no immunosuppression, indicating the potential of our mol. for the treatment of ARDS patients.