Zidane's shock departure came after he had guided Madrid to a third straight Champions League title.
United No 1, De Gea is a long-term target for Real, with the Spanish giants said to be keen on making a mammoth bid for the Spain No 1.
He went on to coach Porto before succeeding Vicente del Bosque, who had overseen Spain's triumphs at the 2010 World Cup and Euro 2012 but had also been in charge for the disappointing group-stage exit at the 2014 World Cup in Brazil.
Whatever did happen, the timing is unfortunate for La Roja as they aim for World Cup glory and also for Los Blancos in their building for the 2018-19 season, while question marks over the coach's suitability for such a top job also persist.
In May, he signed a two-year extension to remain as Spain coach until 2020 but the call of Madrid has proved stronger.
Time will tell, just as it did with Zidane, but right now, the appointment of Lopetegui looks like a risky one for both Madrid and Spain.
Donald Trump Bestows First Post-Summit Sit Down On Sean Hannity
North Korea has called for an end to the exercises as part of the United States' ending its "hostile policy" toward the country. Surprising no one, Fox News confirmed President Donald Trump is giving his first post-summit sit down to pal Sean Hannity .
Breakfast? Nah, IHOb is the International House of Burgers
IHOP's same-restaurant sales - or sales at locations open at least a year - declined 1.9 percent in its most recent fiscal year. A&W, Whataburger , Chili's and Denny's piled on with facetious name-changes and gibes about the new IHOB's burgers.