OBJECTIVES: To validate the Health-Related Productivity Questionnaire (HRPQ), a new health-related productivity instrument, and estimate the US population norms by age and gender. METHODS: An online survey was developed that consisted of four components: the HRPQ; a screener to determine relevant disease conditions-related and health-state questions; validated instruments such as Work Productivity and Activity Impairment (WPAI) and EQ-5D; and socio-demographic questions. The survey was administered by a third-party company for a 6-week period.  Weightings were calculated to allow extrapolation of results from the 10,000 respondents to achieve values representing the general United States population. Validation analysis included concurrent and criterion validity, construct validity with group difference, extreme group comparison and factor analysis. Mean, median, standard error, 25^th and 75^thpercentiles were calculated for absenteeism, presenteeism measures for employed and household work and stratified by age, gender, age and gender. RESULTS: The HRPQ showed strong concurrent validity with WPAI (Pearson’s r≥0.6, p-value<0.05). Correlations of total productivity at work and home from HRPQ with EQ-5D scores, were small to moderate, r=0.3-0.5 (p-value<0.05) and aligned with direction of the hypothesis. Several group difference analyses showed positive results for HRPQ. Presenteeism items heavily loaded on one factor and absenteeism and scheduled hours items loaded on second factor. General population estimates for average percent lost productivity at work was 14%, (absenteeism=4%, presenteeism=10%) and for household activities was 28% (absenteeism=18%, presenteeism=10%). Furthermore, 17% of people reported any kind of loss of workforce participation due to illnesses/treatments. Average work loss productivity was significantly higher in females vs males (16% vs 13%, p<0.05) and decreased with increase in age (20%, 17%, 14%, 11% and 7% in 18-29, 30-39, 40-49, 50-64 and >64 years old, respectively, p-value <0.05). CONCLUSIONS: HRPQ has good construct and criterion validity. Presenteeism remains higher for paid work, while absenteeism remains higher for unpaid work.