Study discovers that adults who sat 11 or more hours each day had a 40 percent increased risk of dying in the following three years compared with those who sat for lesser than four hours a day.
The result was independent of their physical activity, weight and health status.
So, the study of more than 200,000 people suggests standing up more often may reduce the chances of dying within three years, even if you are already physically active.
"These results have important public health implications," said study lead author Dr Hidde van der Ploeg, a senior research fellow at the University of Sydney's School of Public Health.
"That morning walk or trip to the gym is still necessary, but it's also important to avoid prolonged sitting. Our results suggest the time people spend sitting at home, work and in traffic should be reduced by standing or walking more," Dr Ploeg added.
The results are the first landmark findings to be published from the Sax Institute's 45 and Up Study, the largest ongoing study of healthy ageing in the Southern Hemisphere.
They showed physical activity is still beneficial: inactive people who sat the most had double the risk of dying within three years than the active people who sat least. And among the physically inactive group, those who sat the most had nearly one-third higher chance of dying than those who sat least.
The study's size and focus on total sitting time make it an important contributor to the growing evidence on the downsides of prolonged sitting. The average adult spends 90 percent of their leisure time sitting down and less than half of adults meet World Health Organization physical activity recommendations.
Researchers said the evidence was strong enough to support doctors prescribing "reduced daily sitting time" to their patients.
The results have been published in Archives of Internal Medicine.