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Aims: To assess the effects of COVID‐19 pandemic on clinical variables as part of the routine clinical monitoring of patients with chronic diseases in primary care. Design: A prospective longitudinal study was conducted in primary care centres of the Andalusian Health Service. Methods: Data were recorded before the pandemic (T1), during the declaration of the state of emergency (T2) and in the transition phase (T3). The Barthel index and the Short Portable Mental Status Questionnaire (SPMSQ) were used to analyse functional and cognitive changes at the three time points. HbA1c, systolic and diastolic blood pressure, heart rate, BMI and lipid levels were assessed as clinical variables. Descriptive statistics and non‐parametric chi‐square test were used for analysis. STROBE checklist was used for the preparation of this paper. Results: A total fo148 patients with chronic conditions were included in the analysis. Data analysis revealed in T2 only significant reductions in BMI, total levels of cholesterol and HDL during the onset of the pandemic. Barthel Index, SPMSQ, blood pressure and triglycerides and LDL levels worsened in T2, and the negative effects were maintained in T3. Compared to pre‐pandemic values, HbA1c levels improved in T3, but HDL levels worsened. Conclusions: COVID‐19 has drastically disrupted several functional, cognitive and biological variables. These results may be useful in identifying clinical parameters that deserve closer attention in the case of a new health crisis. Further studies are needed to assess the potential impacts of each specific chronic condition. Impact: Cognitive and functional status, blood pressure and triglycerides and LDL levels worsen in short term, maintaining the negative effects in medium‐term. [ABSTRACT FROM AUTHOR]