Objective: This study aimed to compare the anti-inflammatory and antioxidant properties of flaxseed and fish oils as sources of omega-3 fatty acids on lipopolysaccharide (LPS) induced brain injury (BI) in rats. Methods: sixty male albino rats were used in this study and classified into six groups including control, flaxseed oil, fish oil, lipopolysaccharide, treated flaxseed oil and treated fish oil groups. Serum tumour necrosis factor-α (TNF- α) and interleukin – 1α (IL- 1α) were determined by ELISA. Brain malondialdehyde (MDA), superoxide dismutase (SOD) activity, reduced glutathione (GSH) and total antioxidant capacity (TAC) were estimated by colorimetric methods. Brain neurotransmitters were carried out by reversed phase HPLC and UV detection was performed at 270 nm. Immunohistochemistry of cyclooxygenases (COX-1, COX-2) was also performed. Results: The data showed that LPS significantly increased brain MDA, neurotransmitters and COX-2 concomitant with a reduction in brain SOD, GSH, TAC and COX-1. Contrarily, flaxseed and fish oils supplementation improved these values in treated groups. Conclusion: Omega-3 fatty acids in the form of flaxseed and fish oils are considered promising agents in attenuating brain injury and reducing the elevation of brain neurotransmitters due to their antioxidant and antiinflammatory effects.