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Objective: The aim of this study is to investigate the relationship between anxiety due to traumatic brain injury (TBI) and prefrontal cortex serotonin (5-HT) and 5-HT2A receptor in immature rats. Methods: Seven days old rats were subjected to traumatic brain injury model. They were divided into five groups. 1-Sham; 2-TBI group; 3-TBI followed by 14 days of administration of essitalopram (selective serotonin reuptake inhibitors; SSRI) (10 mg/kg) group (TBI+SSRI); 4-TBI and cyproheptadine (nonspecific serotonin receptor antagonist; A) (5 mg/kg) given by gastric gavage one hour prior to behavioral tests (TBI+A); 5-TBI followed by 14 days of essitalopram (SSRI) and cyproheptadine (A) given 1 hour prior to behavioral tests (TBI+SSRI+A). Elevated T-maze test and open field test applied to all groups and then blood corticosterone, prefrontal cortex tissue 5-HT and 5-HT2A receptor quantities measured. Prefrontal cortex neuron density histologically evaluated. Results: In the TBI group, the time spent in the peripheral cells, the time spent in the elevated T-maze closed arms, and serum corticosterone levels found to increase as a result of anxiety. Neuronal density decreased in prefrontal cortex. SSRI treatment reduced the time spent on the closed arms in the elevated T-maze test. SSRI decreased serum corticosterone levels and increased neuronal density. Tissue serotonin levels decreased in all groups exposure to TBI compared to sham group. 5-HT2A receptor levels were higher in the TBI and A group. Conclusion: SSRIs showed anxiolytic effect for anxiety, secondary to TBI in immature rats. [Anadolu Psikiyatri Derg 2019; 20(4.000): 368-376]