Background: Few studies have assessed associations between mental wellbeing (MWB) and productivity loss using nationally-representative longitudinal data. The objective of the study was to determine how different levels of MWB are associated with future productivity loss or costs due to sickness absence. Methods: Data stem from a Danish nationally representative panel study of 1,959 employed adults (aged 16–64 years old) conducted in 2019 and 2020, which was linked to Danish register data. The validated Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS) was used to assess MWB in 2019. The outcome was days absent from work due to sickness in 2020. Linear regression models were used to predict sickness absence in 2020 while adjusting for sickness absence in 2019, sociodemographics and health status, including psychiatric morbidity. Productivity loss or costs were estimated using the human capital approach (HCA) and friction cost approach (FCA). Costs are expressed in USD PPP. Results: Each point increase in MWB was significantly associated with fewer sick days in 2020 and, by extension, lower productivity loss (reported in the order HCA/FCA). As compared to low MWB, moderate MWB was associated with $-1,614/$-1,271 per person in 2020, while high MWB was associated with $-2,351/$-1,779 per person in 2020. Extrapolated to the Danish population (2.7 M employed adults aged 16–64) and as compared to low MWB (12.3% of the population), moderate MWB (67.3% of the population) was associated with lower productivity loss amounting to $-2.9bn/$-2.3bn in 2020, while high MWB (20.4% of the population) was associated with lower productivity loss amounting to $-1.3bn/$-0.9bn in 2020. Conclusions: Higher levels of MWB are associated with considerably less productivity loss. Substantial reductions in productivity loss could potentially be achieved by promoting higher levels of MWB in the population workforce.