The departures come as the shipbuilding business, which owns the yard where the Titanic was built, is beset by challenges.
Malcolm Groat, Sir Jonathon Band and Katya Zotova, all non-executive directors of Harland & Wolff, have resigned from the board with immediate effect.
In recent months, Harland & Wolff has been hit by the loss of a UK government loan and a lucrative contract and only this week said it did not believe the company can finalise its 2023 accounts on a going concern basis.
Work to complete its unpublished accounts has been suspended, with resources being focused on a process with financial adviser Rothschild & Co to identify a route forward that will maximise value for stakeholders and seek to preserve Harland & Wolff's core operations at its delivery centres in Belfast, Appledore, Methil and Arnish.
Concerns have reportedly been raised by investors that these plans could include a pre-pack administration which would wipe out the value of their stakes.
Russell Downs, interim executive chairman, whose appointment was announced last month, said: "On behalf of the board, I wish to thank our outgoing non-executive directors for the time and hard work that they have put in over the years in support of the company and wish them well in their future endeavours."
Harland & Wolff's former chief executive John Wood stepped down last month.