Patients admitted to NHS hospitals on weekends are more likely to die than if they are admitted during the week, according to a new report.
A lack of consultant cover and "reduced" services are contributing to higher death rates, experts behind the study said.
Health Secretary Jeremy Hunt called the research a "wake-up call" and said the situation on weekends may be worse than previously thought.
The study showed that around 11,000 more people die every year within 30 days of admission to hospital on Friday, Saturday, Sunday or Monday compared with other days of the week.
Even when taking into account the fact patients admitted on weekends tend to be sicker, people were still 10% more likely to die if admitted on a Sunday compared to a Wednesday.
For those admitted on a Saturday, there was a 7% increased chance of dying.
Writing in the British Medical Journal, the experts said there was a "clear association" between weekend admissions and worse outcomes for patients.
They said "services inside and outside the hospital are reduced" on weekends, despite the fact there are more emergency admissions on Saturdays and Sundays.
The team, from University Hospital Birmingham NHS Foundation Trusts and University College London, said hospital services "are usually reduced from late Friday through the weekend, leading to disruption on Monday morning".
This could lead to a "weekend effect" extending into Friday and Monday.
They added: "There is evidence that junior hospital doctors feel clinically exposed during the weekend and that hospital chief executives are concerned about levels of weekend cover."
The experts analysed data for almost 15 million patients admitted to hospital in England in 2013/14.
Some 2.7 million patients on average were admitted to hospital on each weekday, 1.2 million on average were admitted on a Saturday and one million on a Sunday.
Mr Hunt, who has warned he is prepared to impose seven-day working on hospital doctors in England, said the research showed the situation may be worse than suspected.
"That's why we urgently need to modernise the contracts for new consultants to make sure NHS patients do not have to worry about a lack of senior clinical presence if they are admitted to hospital on a Saturday or Sunday," he said.
Dr Mark Porter, head of the British Medical Association, said doctors wanted high standard care, seven days a week.
"Urgent action on this has been undermined by calls for the entire NHS to be delivered on a seven-day basis without any clear prioritisation," he said.
"The BMA wants better access to seven-day urgent and emergency care to be the priority for investment.
"This will ensure seriously ill patients receive the best care at all times."
He said as well as extra doctors, there needed to be greater investment in more nurses, diagnostic and support staff.
"David Cameron promised a 'truly seven-day NHS' but there has been no detail to define what he means, how he plans to fund and staff it, and its impact on weekday services.
"Given the current funding squeeze on NHS trusts, the only way for many hospitals to increase the number of doctors over the weekend would be to reduce the number providing care during the week."
NHS medical director, Sir Bruce Keogh, who worked on the study, said doctors went the extra mile but it was unacceptable that patients were harmed due to how services were organised.
He said: "I'm not talking about offering people whatever they want, whenever they want it. The priority is to reduce mortality by concentrating on improving the way we design and deliver urgent care for our sickest patients."
The Royal College of Surgeons president, Clare Marx, said: "It is clear that patients that need treating at the weekend are less likely to be seen by the right mix of junior and senior staff, and experience reduced access to diagnostics.
"Many doctors and NHS staff already work at nights and weekends and they should be valued and thanked for continuing to provide care during those unsocial hours.
"However, the evidence shows that this is not currently standard practice even in high risk emergency care. This has to change."