The aim of this study was to identify the levels of physical activity and sedentary behaviour of children and adolescents with sickle cell disease (SCA) compared to healthy individuals. A cross-sectional study with a quantitative approach was performed at a reference center for the treatment of patients with hemoglobinopathies in northeastern Brazil. Patients were recruited between October 2015 and January 2017. Eligible participants answered a Physical Activity Questionnaire for Older Children and Adolescents (PAQ-C) and were instructed to use an ActiGraph wGT3X-BT triaxial accelerometer for seven consecutive days. Fifty patients (and their 50 controls matched for age and sex) were then evaluated. We observed lower moderate (19.2 ± 11.9 and 27.1 ± 13.8 min/d; p<0.01) and vigorous PA (3.6 ± 4.1 and 7.8 ± 7.4 min/d; p<0.01) in cases than controls, respectively. There was also a significant difference among cases and controls in the following variables: total of steps (51010 ± 19600 and 59105 ± 22650; p = 0.04) and "total caloric expenditure" (1015 ± 516 and 2404 ± 1308; p<0.01), with the lowest values for the patients with SCA for all variables. Children and adolescents with SCA presented lower levels of physical activity than healthy children and adolescents, either when evaluated by PAQs or by accelerometer.