Rett syndrome (RTT) is a neurodevelopmental disorder characterised by, among others, motor impairments, neuroendocrine dysregulation, anxiety altered responses and aberrant pain perception. The primary cause of RTT is de novo loss-of-function mutation in the methyl-CpG-binding domain protein 2 (MECP2) gene, which is located within chromosome X. Although RTT affects mainly females (heterozygous), most rodent studies have used males (hemizygous) as they develop the RTT-associated symptomatology sooner than females (8 weeks vs. 6 months). Here, we analysed both mutant males and females from a CD1 background line at corresponding symptomatic ages, together with control wild-type (WT) siblings. After weighting the animals, they were subjected to an elevated plus maze (EPM) to assess their anxiety responsiveness. One week later, animals received an intraplantar injection of capsaicin to elicit a nociception-specific activation. One hour post-injection, subjects were sacrificed and nervous system collected to assess differential activation in the nociceptive pathway via cFOS immunohistochemistry. Our results show that, although Mecp2 mutant males moved less over the duration of the EPM, they demonstrate a more anxiolytic phenotype than their WT siblings. Mecp2-het females seem to describe a similar behavioural pattern. Nonetheless, mutant females were significantly heavier than their WT siblings while males showed no difference in weight. Following the capsaicin injection, similar changes were observed in both males and females. Together, our results validate this rodent model for the study of RTT-associated neurological manifestation and further demonstrate the need to include animals from both sexes to study the aetiology of RTT and associated disorders.