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Portugal left superstar Cristiano Ronaldo at home, lost their unbeaten record in 2022 and the lead of their UEFA Nations League group.
A goal after 57 seconds by Switzerland forward Haris Seferovic was enough for a 1-0 win in Geneva, despite late pressure by Portugal including two scoring chances for 39-year-old captain Pepe playing as an emergency forward.
Portugal's slip, after letting 37-year-old Ronaldo skip the last game of a long season, let Spain take first place in Group 2 with a 2-0 win over the Czech Republic in top-tier League A.
Goals midway through each half from Carlos Soler and Pablo Sarabia lifted Spain (8) one point clear of Portugal (7) after four rounds.
Portugal had gone unbeaten in five games this year starting with two wins in their World Cup qualifying playoffs in March and including a 4-0 rout of the Swiss last weekend.
Switzerland had gone in the other direction with a five-match winless run since qualifying for the World Cup ahead of group rivals Italy in November.
In Group B4, Erling Haaland made it a 42-goal season tally in all competitions by scoring another double to lead Norway to a 3-2 win over Nordic rivals Sweden.
The 21-year-old striker, who recently signed for Manchester City from Borussia Dortmund, darted in front of a defender to head home his first goal in the 10th minute and converted a penalty early in the second half to make it 2-0.
The 21-year-old star now has 20 goals in 21 senior international appearances with 13 of them scored this season. Haaland also tallied 29 for Dortmund.
Norway leads on 10 points, three clear of Serbia who wasted a two-goal, first-half lead in Slovenia to draw 2-2.
Leaders Greece made it four wins from four by beating second-place Kosovo 2-0 to give coach Guy Poyet's team a six-point lead in the Group C2 standings.
Northern Ireland and Cyprus stayed winless, and each have two points, after their 2-2 draw in Belfast.
In Group C4, Bulgaria drew 0-0 with Georgia (10) who lead the standings by three points from North Macedonia who beat last-place Gibraltar 4-0, while Malta beat San Marino 1-0 in Group D2.