Cancer patients and survivors often experience debilitating cognitive side-effects such as memory impairment, which have been reported up to 20 years post-treatment. Treatment and the anxiety associated with diagnosis have been attributed to these long-term side-effects without consideration that the tumour itself may contribute to cognitive decline seen in cancer patients and survivors. In order to determine the role of the mammary adenocarcinoma and metastasis in cognitive decline and sickness behaviour, we injected 1 x 105 4T1 cells tagged with into the 4th mammary fat pad of Balb/c mice. Tumour growth and metastasis were tracked using bioluminescence imaging. Behavioural assessment for sickness and fatigue-related behaviour were assessed daily and hippocampal-dependent memory performance was assessed weekly. Peripheral and central markers of inflammation were assessed using qRT-PCR. Tumour-bearing mice exhibited poorer performance in memory tasks compared to non-tumour bearing mice from the first week after tumour cell injection. This effect was independent of sickness which only emerged after the onset of metastasis and was related to disease burden. Splenic and hippocampal expression of pro-inflammatory cytokine mRNA was greater in tumour bearing than non-tumour bearing mice and the anti-inflammatory cytokine IL10 was decreased. These findings suggest that peripheral tumours signal the brain, which may contribute to the long-term cognitive decline seen in a subset of patients after treatment. Cytokine expression in the spleen and brain support our hypothesis that the mechanism for this peripheral-to-brain signalling is inflammation.