Ten flights in and out of Belfast and four from Birmingham have been cancelled. Departures from Edinburgh, Newcastle, Southampton, Leeds Bradford and Aberdeen have also been called off.
The airline said it would like to "sincerely apologise for any inconvenience caused".
"All customers affected have been emailed and advised they can rebook for travel on an alternative flight or apply for a full refund," the company said in a statement.
The company has recently moved to a summer timetable however it will not confirm whether this has contributed to the cancellations.
What to do if your flight is cancelled
Flybe’s company statement said, "We have already identified several mitigation actions and will be issuing further updates throughout the day.
"All those affected have been emailed and advised they can re-book for travel on an alternative flight or apply for a full refund."
Flybe's website says that any customers who are at the airport when they find out their flight is cancelled should go to the Flybe customer services desk.
Those who have not arrived at the airport can contact the customer services desk. The UK number is 0371 700 2000. Those outside the UK can call +44 (0)207 308 0812.
On Monday passengers who were supposed to fly on a new route from Newquay to Heathrow were faced with a six-hour replacement coach service after their flight was grounded.
The Scotsman spoke to Fiona Macrae, from consumer awareness campaign, travelinsuranceexplained.co.uk gives advice on what you can expect from your travel insurance if you have been affected by the cancellations.
She said: “Under European Legislation there is also a ‘re-route’ option which means that if your original airline cannot get you to your destination on your booked date, or the day after then you can demand to be booked with a rival airline (subject to seat availability) – your original airline is legally responsible for booking replacement flights and should bear the cost accordingly.
“If the airline advises you to make your own arrangements then provided you can prove that you have taken the only available alternative, you should be able to reclaim the costs from the original airline.
“Unfortunately travel insurance policies do not cover the cost of a replacement flight; you should therefore make use of the ‘re-route’ option mentioned above.”
On potentially cancelling flights, Fiona said: “If you are unable to make alternative travel arrangements, you may wish to cancel your holiday altogether.
“However you should be aware that most travel insurance policies only cover cancellation due to ‘specified reasons’ and the cancellation of flights by an airline is not usually a specified reason.
“However, if you have a travel insurance policy which offers cancellation cover for ‘any cause beyond your control’ or anything ‘which you could not have been expected to foresee or avoid’ you may be able to cancel your holiday and claim back any pre-paid expenses, such as excursions, car hire costs or accommodation fees that you cannot get back from anywhere else.”