Disruption of sleep and circadian rhythms has been implicated in cancer progression and cancer-related side-effects, such as cognitive impairment and depression. Sleep disruption is commonly reported in cancer patients and survivors. This study examined the role of circadian disruption on cancer progression, cognition and depression-like symptoms in a mouse model of metastatic breast cancer. 80 female mice were placed on either a stable 12 h light:dark schedule or a rotating light cycle that advanced by 8 h every two days to induce chronic jet-lag, comparable to the impact of shift work. Mice were injected with 4T1.2 mammary adenocarcinoma cells or given a sham injection of PBS into the 4th left mammary fat pad. Tumour cells were tagged with luciferase so that bioluminescence imaging could be used to track tumour growth and metastasis. Running wheel activity was used as a marker of circadian disruption, as well as overall activity levels. Circadian disruption profoundly impacted cancer progression by increasing both primary tumour growth and metastasis (p < 0.05). Behavioural assessments of depression (using the forced swim and sucrose preference tests) and memory (using the novel object recognition test) were assessed as circadian disruption and cancer progressed. Circadian disruption and tumours each independently impaired memory (p < 0.05). Circadian disruption alone induced depression-like behaviour on the sucrose preference test that was not exacerbated by cancer (p < 0.05), confirming our preclinical findings and clinical studies indicating that depressive symptoms are not correlated with cognition symptoms driven by the cancer. These findings demonstrate that circadian disruption seen in cancer patients and vulnerable populations such as shift workers can drive cancer progression and impact cancer-associated side-effects. The results of this preclinical model of circadian disruption and metastatic breast cancer, in the absence of psychosocial factors and cancer treatments, identify the need for clinical studies to dissociate poor sleep from circadian rhythms when assessing these factors in cancer-related outcomes.