As expected, the striker is not included in the match squad of 22 for the penultimate friendly of the summer.
It comes after the wantaway striker has been made to train alone at Benton this week amid anger and disappointment at the 25-year-old's conduct amid transfer interest from Liverpool.
Isak wasn't part of the Newcastle squad for their pre-season camp in Asia and instead headed to Spain to train alone at his former club Real Sociedad, without Eddie Howe's consent.
Since returning to the UK at the weekend, Isak has trained alone. He isn't involved tonight and isn't expected to play any part in Saturday's game against Atletico Madrid.
In Isak's absence, Will Osula will lead the line for Newcastle against Espanyol, with Howe naming a strong starting XI.
Aaron Ramsdale makes his first Newcastle start, as does South Korean youngster Seung-soo Park.
Emil Krafth, Fabian Schar, Dan Burn and Matt Targett line up in defence. Lewis Hall will play in midfield alongside Lewis Miley and Bruno Guimaraes, with Jacob Murphy and Seung-soo Park supporting Osula.
Howe has named a youthful bench, with Garang Kuol and Alex Murphy the more experienced of the substitutes.
Cathal Heffernan, Scott Bailey and Dylan Charlton are also named, along with Leo Shahar, Alfie Harrison, Trevan Sanusi and Sean Neave.
John Ruddy and Mark Gillespie are the substitute goalkeepers.
_**Newcastle: Ramsdale; Krafth, Schär, Burn, Targett; Miley, Guimarães, Hall; Murphy, Osula, Seung-soo**_
_**Substitutes: Ruddy, Gillespie, Shahar, Heffernan, Murphy, Bailey, Charlton, Harrison, Sanusi, Kuol, Neave.**_