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The 27-year-old Briton is expecting her first baby with husband Andy, but still plans to defend her Olympic gold medal at the 2016 Rio Games.
"I am sorry I won't be in Glasgow for the Commonwealth Games," she said.
"But I know it will be an amazing occasion. I will be at home awaiting the arrival of a little Ennis-Hill."
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England's Ennis-Hill won bronze at the 2006 Commonwealth Games in Melbourne and chose to skip the 2010 Games in Delhi to concentrate on the European Championships the same year, where she won gold.
Her announcement means she will also miss the 2014 European Championships in Zurich.
The 2009 world champion, who got married in May 2013, added: "We are completely overwhelmed, with excitement and a degree of anxiety that I am sure all first-time parents will relate to.
"My plans for 2014 have been completely turned upside down, but having had a couple of weeks to think about things from a career point of view I am 100% set on returning to full-time athletics once our baby is born and go for a second gold medal at the Rio Olympics in 2016. That challenge really excites me.
"But, in the short-term, I will make our baby a priority and enjoy the whole experience as much as possible."
"The Glasgow 2014 team sent on their congratulations but it is difficult to view the news as anything other than a blow for them.
It has been a positive few months for the organisers, with news that 94% of the tickets have already been sold and updates suggesting venues are on track and finances on budget.
"Just who attends, though, is something mostly out of their control, but after the news there will be no Jessica Ennis-Hill, fingers will be crossed in Glasgow that Usain Bolt and Mo Farah make an appearance."
Despite suffering a disappointing 2013 season where she missed the World Championships because of an Achilles tendon problem, London 2012 Olympic champion Ennis-Hill was favourite for gold in Glasgow.
Former Great Britain 400m runner Katherine Merry backed Ennis to defend her Olympic title at the Rio Olympics but British 2010 Commonwealth heptathlon champion Louise Hazel believes there must be some doubt over Sheffield athlete Ennis staying in the multi-discipline event.
Hazel, who has now retired from heptathlon, said: "Is it possible to be an elite sportswoman and have a baby? Yes.
"Is it possible to come back from Olympic gold as a heptathlete and go on to Rio... it throws a huge question over the continuation of a career as a heptathlete and that's just being realistic."
Merry also suggested that 2014 was a good year to have a break from the sport.
"Without being demeaning to other major championships, if there was going to be a year when an athlete of her stature was going to miss, it would be a year when the Commonwealths and Europeans fall," Merry told BBC Radio 5 live.
"In terms of ranking, they don't sit alongside the Worlds and the Olympics, so it will fall very nicely in terms of her getting back and the timescale of going to Rio to defend that London Olympics gold.
"It's a huge [decision], especially for British athletes because they don't have a year off. We have a major championships every year."
Merry, who won bronze at the 2000 Olympics in Sydney, added: "The key thing is what fitness you do during pregnancy. Many athletes like [former world marathon champion] Paula Radcliffe were running well into her pregnancy and keeping very fit and I'm sure Jess will do the same and keep herself ticking over to make the return a bit easier."
David Grevemberg, chief executive of Glasgow 2014, said: "I would like to warmly congratulate both Jessica and her husband Andy on the news that they are expecting their first child.
"Glasgow 2014 is proud to have Jessica as an inspiring ambassador for the Games and appreciate her continued support for the world-class festival of sport which Glasgow and Scotland will host this summer."
Team England chef de mission Jan Paterson also congratulated the pair, adding: "Jessica is a wonderful athlete and role model and I'm sure she'll be cheering on the team in Glasgow 2014. "
Olympic heptathlon champion Jessica Ennis-Hill will miss the Commonwealth Games in Glasgow because she is pregnant.