Background: High vaccination coverage rates are necessary to reduce infections and transmissions of the SARS-CoV-2 virus causing COVID-19 and to allow successful mitigation of the current pandemic. To date, we are still lacking information to explain the hesitancy in Luxembourg towards uptake of the available COVID-19 vaccines. The present study explored motivations for and against vaccination in a population-representative sample of residents across Luxembourg to identify hesitant groups and develop strategies to increase population immunity against SARS-CoV-2. Methods: In the framework of the nationwide, representative longitudinal CON-VINCE study, a sample of 1589 respondents (49.6% women, 84.3% Luxembourg nationality) ranging from 18-84 years, participated in the survey in spring 2021. The protocol of the CON-VINCE study has been described in detail elsewhere (Snoeck et al. 2020). Results: 52% of the respondents had at least partial vaccination at time of assessment between April to June 2021. The most common reasons for vaccination of those willing to be vaccinated (81.2%) were altruistic motivations. Prevalent reasons against vaccination for those undecided (8.7%) or reluctant (10.2%) to be vaccinated were that the vaccine had not been tested sufficiently and the fear of long-term vaccine side effects. Only very few of the vaccination-hesitant or -reluctant respondents reported that they did not believe in vaccination in general. Conclusion: The present study identified motivations for and against COVID-19 vaccination and determined demographic and socio-economic factors associated with vaccination willingness. To increase vaccination rates, public health communication needs to target those unsure or unwilling to be vaccinated. We will continue to study the vaccination uptake in the Luxembourg population, as CON-VINCE is now part of the H2020-funded international ORCHESTRA project (https://orchestra-cohort.eu), research into comparing these results on a Pan-European level.