This study aimed to evaluate the cardiometabolic effects of a home-based lifestyle intervention (LI) in breast cancer survivors (BCSs) during the COVID-19 lockdown. In total, 30 BCSs (women; stages 0-II; non-metastatic; aged 53.5 ± 7.6 years; non-physically active; normal left ventricular systolic function) with a risk factor for recurrence underwent a 3-month LI based on nutrition and exercise. Anthropometrics, Mediterranean diet adherence, physical activity level (PAL), cardiorespiratory fitness (VO_2max), echocardiographic parameters, heart rate variability (average standard deviation of NN intervals (ASDNN/5 min) and 24 h very- (24 hVLF) and low-frequency (24 hLF)), and metabolic, endocrine, and inflammatory serum biomarkers (glycemia, insulin resistance, progesterone, testosterone, and high-sensitivity C-reactive protein (hs-CRP)) were evaluated before (T0) and after (T1) the LI. After the LI, there were improvements in: body mass index (kg/m²: T0 = 26.0 ± 5.0, T1 = 25.5 ± 4.7; p = 0.035); diet (Mediet score: T0 = 6.9 ± 2.3, T1 = 8.8 ± 2.2; p < 0.001); PAL (MET-min/week: T0 = 647 ± 547, T1 = 1043 ± 564; p < 0.001); VO_2max (mL·min^-1·kg^-1: T0 = 30.5 ± 5.8, T1 = 33.4 ± 6.8; p < 0.001); signs of diastolic dysfunction (participants: T0 = 15, T1 = 10; p = 0.007); AS-DNN/5 min (ms: T0 = 50.6 ± 14.4, T1 = 55.3 ± 16.7; p = 0.032); 24 hLF (ms²: T0 = 589 ± 391, T1 = 732 ± 542; p = 0.014); glycemia (mg/dL: T0 = 100.8 ± 11.4, T1 = 91.7 ± 11.0; p < 0.001); insulin resistance (HOMA-IR score: T0 = 2.07 ± 1.54, T1 = 1.53 ± 1.11; p = 0.005); testosterone (ng/mL: T0 = 0.34 ± 0.27, T1 = 0.24 ± 0.20; p = 0.003); hs-CRP (mg/L: T0 = 2.18 ± 2.14, T1 = 1.75 ± 1.74; p = 0.027). The other parameters did not change. Despite the home-confinement, LI based on exercise and nutrition improved cardiometabolic health in BCSs.

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