Adolescence, a critical stage of development characterized by increased neuroplasticity, is marked by a significant risk for the onset of psychiatric disorders. Inflammatory events during this period may increase the risk of developing psychiatric disorders, with tryptophan metabolism playing a potential role in this process.Our goal was to investigate whether exposure to lipopolysaccharide (LPS) during adolescence impacts emotional behaviour and the inflammatory response in adult animals in a sex-specific manner. Male and female C57BL6J mice were injected at PND36 with LPS (0.1 mg/kg i.p.) or saline. At 12 weeks, mice again randomly received either LPS (0.83 mg/kg i.p.) or saline. 24h later animals were tested in a Y-maze and sacrificed. Serum levels of serotonin (5HT), tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA) were measured by HPLC-MS/MS.Adult male mice receiving LPS showed a significant decreased ratios for 5HT/TRP and KYNA/KYN and an increased KYN/TRP ratio, regardless of the treatment received during adolescence. In contrast, in adult females, tryptophan catabolism was less affected by LPS exposure: the 5HT/TRP ratio remained stable, while effects similar to those in males for KYNA/KYN and KYN/TRP were observed only in females exposed to LPS both in adolescence and adulthood.Adolescent LPS treatment potentiated the behavioural effects of the immune challenge experienced in adulthood especially in female animals: a double LPS exposure led to considerable impairments in y-maze short-term spatial memory tests.These results underscore the importance of sex and early-life adverse events in determining the molecular and behavioral outcomes of immune challenges in adulthood.