Szafnauer will leave by “mutual agreement” after this weekend’s Belgian GP.
Alpine noted that he “will continue his duties as normal for this weekend’s race in Belgium, before leaving the team ahead of the summer break.
“The team would like to thank Otmar for his hard work over the past 18 months and for leading the team in achieving fourth place in the 2022 constructors' championship. The team wishes him the best for the future.”
He will be replaced on an interim basis by Bruno Famin, who was named earlier this month in newly created role of VP of Alpine Motorsport.
Before his recent appointment Famin was the head of the Renault operation in Viry-Chatillon, having previously worked at Peugeot and the FIA.
Alpine sporting director Alan Permane, who has been with the Enstone organisation in a variety of roles for 34 years, is also leaving the team after the break. He will be replaced Alpine Academy director Julian Rouse on an interim basis.
The changes come in the wake of a recent major management shake-up across the Alpine company initiated by overall Renault boss Luca de Meo that saw CEO Laurent Rossi, Szafnauer’s erstwhile boss, moved into special projects.
The 58-year-old Szafnauer joined Alpine in February last year having left the team principal role at Aston Martin just a few weeks earlier.
He had been with the Silverstone team since 2009 through its Force India and Racing Point eras, before leading the transition to Lawrence Stroll’s ownership and the subsequent rebranding of the team as Aston Martin.
Despite his imminent departure, Szafnauer represented Alpine in Friday’s meeting of the F1 Commission at Spa.
Only last week in Hungary the American said that he had faith in De Meo, confirming that the Renault boss had given him 100 races to make the team a race winner.
“You’ve got to remember that Laurent is doing special projects now,” said Szafnauer when asked by Motorsport.com about the impact of Rossi’s move.
“Yes, he did hire me, but Luca also hired me, and it was Luca de Meo who ultimately sat down with me and convinced me to join his project.
“And the project was the Alpine project with the 100-race plan, and I think we are 30-something races into that. So we still have some 60-odd races to go, and that is another three years to go to start winning.
“It takes time. It has taken everybody time. I know Luca is a man of his word, and he gave me his word on 100 races to start winning, and sometimes you take a half-step backwards to take two steps forward.
“So I have no concern that Luca will be true to his word and give me the 100-races time that is required.”
Permane originally joined the then Benetton team in 1989 as an electronics engineer. He was thus part of the team all the way through the Michael Schumacher era, which included world championships for the German in 1994 and 1995.
He became a junior race engineer in 1996 and a full race engineer the following year, working with a variety of drivers over a spell that saw the team win two more titles with Fernando Alonso in 2005 and 2006.
He became chief engineer in 2007 and then sporting director in 2012. Having stayed with the team through its Lotus days to the return to Renault ownership and the rebadging as Alpine he still holds that role.
In a move unrelated to the rest of the Alpine shake-up, chief technical officer Pat Fry is set the leave the Enstone camp to join Williams in a similar role by the end of this year.