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Background: Restrictions during Covid-19 pandemic lockdown, in which rhythms of life have been compromised, can influence the course of bipolar disorder (BD). This study follows patients with bipolar disorder living in two geographically close cities (Cagliari and Tunis), but with different lockdown conditions: less severe in Tunis. Methods: Two cohorts were evaluated during lockdown (April 2020, t0) and 2 months later with lockdown lifted for a month (t1). Individuals were: over 18 years old without gender exclusion, BD I or II, in care for at least 1 year, received a clinical interview in the month before the start of the lockdown, stable clinically before the lockdown. The assessment was conducted by telephone by a psychiatrist or psychologist with good knowledge of patients. Diagnoses were made according to DSM-5 criteria. Depressive symptoms were collected through the Hamilton Rating Scale for Depression; cut-off 14 indicative of depressive episode. Circadian rhythms were measured using the BRIAN scale. Results: Forty individuals in Cagliari (70%female, age 48.57 ± 11.64) and 30 in Tunis (53.3% Female, age 41.8 ± 13.22) were recruited. In Cagliari at t0 45% had depressive episodes against none in Tunis, a similar difference appeared at t1. At t0 and t1 the Cagliari sample had more dysfunctional scores in the overall BRIAN scale and in the areas of sleep, activities and social rhythms; no differences were found in nutrition, both samples had predominantly nocturnal rhythm. In Cagliari at t0 and t1, the depressive sub-group showed more dysfunctional scores in the BRIAN areas sleep, activity, and nutrition. However, the differences in biological rhythms resulted, through ANCOVA analysis, independent of the co-presence of depressive symptoms. Discussion: A rigid lockdown could expose people with BD to depressive relapse through dysregulation of biological rhythms. The return to more functional rhythms did not appear 1 month after lockdown. The rekindling of the pandemic and the restoration of new restrictive measures will prevent, at least in the short term, the beneficial effect of a return to normality of the two cohorts. This was a limited exploratory study; future studies with larger samples and longer observational time are needed to verify the hypothesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Carta, Ouali, Perra, Ben Cheikh Ahmed, Boe, Aissa, Lorrai, Cossu, Aresti, Preti and Nacef.)