Abstract Background Epidemiological studies show that long-term exposure to ambient air pollution reduces life expectancy. Most studies have been in environments with relatively high concentrations such as North America, Europe and Asia. Associations at the lower end of the concentration-response function are not well defined. Objectives We assessed associations between all-cause mortality and exposure to annual average particulate matter <2.5 μm (PM 2.5) and nitrogen dioxide (NO 2) in Sydney, Australia, where concentrations are relatively low. Methods The '45 and Up Study' comprises a prospective longitudinal cohort from the state of New South Wales, Australia with 266,969 participants linked to death registry data. We analyzed data for the participants who resided in Sydney at baseline questionnaire (n = 75,268). Exposures to long-term pollution were estimated using annual averages from a chemical transport model (PM 2.5), and a satellite-based land-use regression model (NO 2). Socio-demographic information was extracted from the baseline questionnaire. Cox proportional hazard models were applied to estimate associations, while adjusting for covariates. Results In our cohort mean annual PM 2.5 was 4.5 μg/m3 and mean NO 2 was 17.8 μg/m3. The mortality rate was 4.4% over the 7 years of follow up. Models that adjusted for individual-level and area-level risk factors resulted in a detrimental non statistically significant hazard ratio (HR) of 1.05 (95% CI: 0.98–1.12) per 1 μg/m3 increase in PM 2.5 , and 1.03 (95% CI: 0.98–1.07) per 5 μg/m3 increase in NO 2. Conclusions We found evidence that low-level air pollution exposure was associated with increased risk of mortality in this cohort of adults aged 45 years and over, even at the relatively low concentrations seen in Sydney. However, a clear determination of the association with mortality is difficult because the results were sensitive to some covariates. Our findings are supportive of emerging evidence that exposure to low levels of air pollution reduces life expectancy. Highlights • We report new information on the effects of long-term exposure to low levels of ambient air pollution on mortality • PM 2.5 and NO 2 had detrimental but non statistically significant associations with all-cause mortality at low concentrations • Our results were larger than comparable studies in higher pollution environments but were variable under the model sensitivity test • Exposure measurement error and other statistical issues complicate studies of air pollution concentrations at this low end of the spectrum • It is unknown if there is any safe low threshold of air pollution for health, and this is important as many countries strive to continuously reduce air pollution emission levels to protect public health [ABSTRACT FROM AUTHOR]