Oxford Station will close for nine days between Saturday, July 29 and Sunday, August 6.
The closure is to allow upgrades to the track and signalling system to take place.
There will also be a number of overnight and one-day closures before and after the core works.
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Overnight works will take place from 11pm on Saturdays until 08.40am on Sundays every week from June 3 to July 16.
One-day closures will also affect train services in the Oxford area on the following days:
Sunday, August 13
Sunday, September 10
Sunday, October 15
No trains will run to and from Oxford Station on these dates.
Rail replacement buses will run from Didcot, Banbury, Leamington, Hanborough and Oxford Parkway.
Trains will continue to run between London Paddington and Didcot Parkway.
Oxford Parkway will also remain open.
Great Western Railway service has advised passengers to check carefully before travelling as departure times will be different to normal.
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