Background: Patients with bipolar disorder (BD) are at increased risk of cardiovascular disease (CVD). While exact mechanisms have yet to be elucidated, inflammation has been identified as a potential contributing factors to disease etiology and pathogenesis. Obesity is also associated with a chronic inflammatory response characterized by abnormal cytokine and adipokine production, increased synthesis of acute-phase reactants such as C-reactive protein (CRP), and the activation of pro-inflammatory signaling pathways. Methods: We examined alterations in plasma levels of the cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and CRP and the adipokines leptin, adiponectin and resistin longitudinally over two years in 25 patients with BD who were medication naive at study enrolment. Results: Over 2-years of follow-up, we observed significant increases in TNF-alpha, CRP, IL-6 and leptin and significant decreases in resistin and adiponectin (p<.05). These changes were associated with increases in waist circumference and improvement in symptom severity (p<.05). Conclusion: Our results suggest that cytokines and adipokine levels change over time in patients with BD. These changes, which appear linked to weight gain, may contribute to increased cardiovascular illness in patients with BD. These findings highlight the need to implement weight management interventions early in treatment.