Pathophysiology associated with acute respiratory distress syndrome (ARDS) extends beyond acute lung injury (ALI) to the brain causing cognitive impairments in ARDS survivors. Aims: To evaluate the contributions of oxidative stress and neuronal nicotinic receptors to pulmonary ALI-induced behavioral changes. Material and Methods: Male BALB/C mice received intratracheal saline or lipopolysaccharide (LPS, 5mg/Kg). After 24hs, short-term memory was assessed by novel object recognition task (NORT) then lung, bronchoalveolar lavage fluid, and brain were collected for evaluation of signs of inflammation, oxidative markers, and/or nAChR expression. Data were analyzed with t-test with p<0.05 considered significant. Results: LPS induced larger fractional of collapse/hyperinflated and shorter fractional of normal lung area, increased wet/dry weight ratio, neutrophils, the levels of IL-6, TNF-? and KC in bronchoalveolar lavage fluid compared to control. In NORT test sessions, LPS-treated mice spent less time exploring the new than the familiar object, indicating a memory deficit. LPS treatment increased glutathione peroxidase activity, nitrite levels in the cerebellum, and superoxide dismutase activity in the hypothalamus. LPS treatment reduced ?7 and ?4 nAChRs mRNA expression in the cortex and hippocampus and ?2 nAChR mRNA expression in the cortex and cerebellum. Conclusion: ALI induced by pulmonary insult leads to an impairment in short-term memory that can be related to increased oxidative stress and reduced nAChR expression in the brain, suggesting that peripheral inflammation per se would be a stimulus for the deterioration of cognitive functions.