Trains from Hemel Hempstead and Clapham Junction have been cancelled for the rest of the day because of staff shortages caused by sickness and a staff training day.
Rail operator Southern Rail said that the problem was caused by a combination of staff calling in sick at short notice and a number of drivers training for the new track layout
Passengers are advised to use London Midland between Euston and Milton Keynes Central, or the London Overground or Underground.
A Southern Rail spokesman said: “We would like to apologise to our passengers for the cancellation of Southern services between Milton Keynes and London today.
“There has been an unusually high amount of short- notice sickness and, coupled with some of our drivers training for the new track layout at London Bridge in January, we do not have drivers available to provide most of the service.
“However, Southern tickets are being accepted on London Overground, London Midland and London Underground services, so passengers will be able to get to their destinations without problems.”