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Anxiety disorders form one the most common type of mental illness and comprises of separation anxiety, specific phobias, social anxiety disorder, and generalized anxiety disorder. These disorders offer considerable comorbidity with other mental disorders like depression, memory and learning deficit which all shows considerable seasonal variance. Seasonal changes have major impact on health of individuals' especially mental health. N-Acetylcysteine (NAC) is an acetylated derivative of cysteine, and is considered as an antioxidant precursor to glutathione. It has been shown to ameliorate various types of mental disorders. This study investigated changes in anxiety-like behaviours in albino mice across different seasons in Nigeria and the modulatory role of NAC. The study was conducted across two seasons (cold dry and hot humid seasons) Nigeria. Forty (40) mice of both sexes (20/season) were used, divided into control (normal saline) and NAC (500mg/kg body weight) groups, respectively. All administration was done orally for one week and the rectal temperatures were measured. Behavioural test was conducted using Elevated Plus Maze (EPM) and Open Field Test under standard protocols for each season for a period of one week. The parameters for seasonal changes were also recorded. All analyses were done using Mixed ANOVA followed by Tukey's and Bonferroni's test, respectively and (P-values <0.05) were considered significant using SPSS version 22. The results of the study revealed a significant (P < 0.05) increase in anxiety-like behaviours in hot humid season and increased locomotive activity in cold dry season in male mice. Female mice were more susceptibility to anxiety in cold dry season, which was ameliorated by NAC. In conclusion, the study revealed that hot humid season have anxiogenic like effects, while cold dry season increased locomotive activities in male mice, demonstrating increase exploratory activity and decrease in level of anxiety. The study establishes the occurrence of anxiogenic-like behaviours in female mice in the cold dry season which was ameliorated by NAC administration. Key Words: Anxiety, Seasonal Variation, N-Acetyl Cysteine, Neurobehaviour Running Title: Seasonal variation and Anxiety-like behaviour.