Second generation antipsychotics (SGAs) are the first line treatment for psychosis and schizophrenia. SGAs are efficacious in reducing symptoms of these neuropsychiatric conditions; however, they are associated with metabolic side-effects that can be detrimental to a patient’s health and well-being. Patient’s taking SGAs have a three-fold increased risk of developing metabolic syndrome (MetS). MetS includes the development of type 2 diabetes, unprecedented weight gain, and dyslipidaemia. We hypothesised that SGAs disrupt mitochondrial function in the brain and periphery, and this may explain the development of MetS seen with SGA treatment. We assessed mitochondrial function in neuroblastoma (SH-SY5Y) and hepatoma (HepG2) cell lines treated with olanzapine, clozapine, and aripiprazole. Olanzapine is known to have the highest propensity to trigger MetS, and aripiprazole, the lowest. Co-treatment with metformin was also investigated to understand whether metformin attenuates the effects of SGAs on mitochondria. Mitochondrial function was assessed via high resolution respirometry using the O2k Oxygraph (Oroboros Instruments). Lipid droplet (LD) accumulation can indicate an increase in oxidative stress, or an altered state of nutrient supply to the cell which may be triggered by SGA treatment. Therefore, LD formation was assessed in the cell lines. Alterations in mitochondrial function and LD formation, potentially induced by SGAs, can lead to metabolic abnormalities that exacerbate pre-existing conditions or trigger the development of MetS. The ultimate aim is to develop a personalised medicine approach and identify the optimal dose, drug, or polypharmacy to effectively treat psychosis while minimising the risk of MetS for the individual.