Abstract Background Since the onset of the COVID-19 pandemic, most research has focused on the acute phase of COVID-19, yet some people experience symptoms beyond, referred to as post COVID-19 conditions (PCC). However, evidence on PCC and its impacts on health-related quality of life (HRQoL) is still scarce. This study aimed to assess the impact of COVID-19 and PCC on HRQoL. Methods This is a longitudinal cohort study of the Belgian adult population with recent SARS-CoV-2 infection. In total, 5,727 people were followed up between the time of their infection and three months later. HRQoL was measured with the EQ-5D-5L questionnaire before and during the infection and three months later. Linear mixed regression models were built to assess the longitudinal association between participants’ characteristics and the evolution of their HRQoL. Results This study found a significant decline in HRQoL during the SARS-CoV-2 infection in comparison to the situation before (β=-9.91, 95%CI=-10.13;-9.85), but no clinically important difference three months after the infection compared to the situation before, except among people reporting PCC (β=-11.15, 95%CI=-11.72;-10.51). The main symptoms of PCC with a significant negative impact on the different dimensions of HRQoL were fatigue/exhaustion (21%), headache (11%), memory problems (10%), shortness of breath (9%), and joint (7%) or muscle pain (6%). The dimension of HRQoL most negatively affected by several PCC symptoms was pain/discomfort. Conclusions With the growing number of people infected with SARS-CoV-2, PCC and its impact on HRQoL are becoming important public health issues. To allow people with PCC to recover and to limit its detrimental impact on HRQoL, it is essential to manage its various heterogeneous symptoms using a multidisciplinary approach.