Background: Prior studies in bipolar disorders (BD) have suggested that oxidative stress and cellular ageing play a key role in the pathophysiology of BD. Nevertheless, oxidative stress has not been investigated in patients with newly diagnosed BD and in their unaffected first-degree relatives (UR), compared with healthy control individuals (HC). Methods: We investigated the level of systemic oxidative damage to DNA and RNA measured by urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) levels, respectively, in 360 patients with newly diagnosed BD, 92 of their UR and 197 HC. Results: Independent of lifestyle and demographic variables, levels of both 8-oxoGuo and 8-oxodG was 17.1% (B = 1.171, 95%CI = 1.125–1.219, p < 0.001) and 21.2% (B = 1.212, 95%CI = 1.145–1.283, p < 0.001) higher, respectively, in patients with BD compared with HC and 13.3% (B = 1.133, 95%CI = 1.069–1.200, p < 0.001) and 26.6% (B = 1.266, 95%CI = 1.167–1.374, p < 0.001) higher, respectively, in UR compared with HC. Neither 8-oxoGuo nor 8-oxodG levels differed between patients with BD and UR. These findings were replicated in patients in full or partial remission and were consistent both in BD type I and II. Conclusion: Overall, the findings of higher oxidative stress in patients with newly diagnosed BD and their UR suggest that systemic nucleoside damage by oxidative stress is present prior to onset and in the early stages of BD thereby potentially representing trait markers of BD.