Dragons chief executive Andy Marinos is leaving his position at Rodney Parade.
"Recent events forced me to consider my future here," said the South African born, former Wales centre.
"I now feel that the time is right to return to South Africa and look to explore other opportunities, hopefully within rugby.
"While retaining a wish to play a role driving the region forward, I feel I have to look after the best interests of my family and I."
Marinos has been at Newport for six years, first as a player before becoming chief executive at the end of the 2003/4 season.
Welsh Rugby Union chief executive David Moffett said he regretted Marinos' departure and revealed the first steps to find a successor have already begun.
"[WRU general manager] Steve Lewis will be seeking urgent meetings with the Dragons to find out where exactly they are going," Moffett told BBC Wales Sport.
"They've had a succession of coaches and chief executives over the last few years. They are a terribly important team for Wales and its a very important regions for Wales.
"We need to be confident that with all the changes taking place they will be able to take their rightful place as one of the major forces behind the resurrection of Welsh rugby."
The Dragons will undergo a major overhaul at the end of the season, with coach Chris Anderson departing and benefactor Tony Brown withdrawing his financial support.
Star back Percy Montgomery is also expected to leave for either France or his native South Africa.
"I wish to thank the players, directors, staff, supporters and sponsors who have supported me throughout my time here, with special thanks to Tony Brown who facilitated my move to Newport in the first place," added Marinos.
"While the transition to regionalisation has not always been smooth, the region has finished third and fourth respectively in the last two seasons.
"Last year Newport RFC won the Premiership and this year look to finish second.
"I sincerely hope by putting financial and procedural policies in place and presenting a balanced budget for the 2005/06 season that whoever takes over will be able to take the region and club forward.
"I wish them and both teams at Rodney Parade every success for the future."