Indoor vaping can lead to third-hand vapour exposure, evidenced by the presence of nicotine and carcinogenic nitrosamines on indoor surfaces. Children are at high risk of such exposure. This study aimed to investigate the effects of third-hand vapour exposure on cognitive function in young mice. Male mice (Balb/c, 4 weeks) were exposed to cotton towels treated with e-cigarette vapour with and without nicotine (9 L chamber filled with 20 puffs of vapour for 2 hours) and changed daily for four weeks. Vapour was generated from tobacco-flavoured e-cigarette liquids (50 % propylene glycol, 50 % vegetable glycerine, 18 mg or 0 mg nicotine) using a human e-cigarette device. Mice exposed to nicotine-free vapour showed impaired short-term memory, while those exposed to nicotine-containing vapour exhibited significantly increased anxiety-like behaviours. Both exposure groups had reduced neuron numbers in the cortex and increased microglia numbers and pro-inflammatory cytokine expression in the brain. Third-hand exposure to vapour can impair memory function and increase anxiety, with some effects being nicotine-independent. These findings highlight the potential risks of indoor vaping, especially in environments frequented by younger people, including children and adolescents, and the need for further research to identify the underlying mechanisms. SYNOPSIS: This is the first study highlighting the risks of cognitive impairment due to third-hand exposure to e-cigarette residues in a mouse model.