Facebook shares are likely to fall significantly in the short term due to the departure of two key executives, according to J.P. Morgan.

Facebook confirmed a report by The New York Times on Monday that the co-founders of Instagram, Kevin Systrom and Mike Krieger, had resigned from Facebook.

Shares of Facebook fell as much as 2.6 percent Tuesday before paring its loss for the session to down 0.1 percent.

"We believe their departure comes as a surprise given Instagram's success and its growing importance within Facebook," J.P. Morgan analyst Doug Anmuth said in a note to clients Tuesday. "We look for additional color in coming days and weeks, but in the near-term, we expect FB shares to come under meaningful pressure from the departures."

Instagram has more than 1 billion monthly active users. Anmuth estimated the photo-sharing app will generate about $7.5 billion of sales for Facebook this year and represent 14 percent of the company's ad revenue.

"We believe Instagram has been a strong growth driver for FB and has played a critical role in retaining younger users within the group of FB platforms and in competing w/Snap," the analyst said.

Anmuth maintained his overweight rating and $195 price target for Facebook shares in the report.

— CNBC's Michael Bloom contributed to this story.