Valencia striker David Villa has torn a thigh muscle and will be out of action for around three weeks, the La Liga club said on Monday.
"A new test will be carried out in seven days, but in the meantime the estimated recovery time is three weeks," Valencia said in a statement on their website (www.valenciacf.com).
Villa, La Liga's top scorer with six goals, was substituted during his side's 1-0 win over Racing Santander on Sunday and will miss Spain's World Cup qualifiers in Armenia and Bosnia on Oct. 10 and 14.
The European champions have qualified for next year's finals.
Valencia will be without Villa for the visit of champions and league leaders Barcelona in two weeks' time.
Pires urges slumping Villarreal to keep the faith
Meanwhile, the break for internationals will give struggling Villarreal time to clear their heads and take stock for the return to La Liga action in two weeks' time, French midfielder Robert Pires said on Monday.
Villarreal are 19th in the 20-team league with three points from a possible 18, and are still seeking their first win of the campaign.
"These 15 days will be good for us to disconnect from the situation a little, and to prepare for the upcoming games. For me, these will be crucial," the former Arsenal player, 35, told a news conference.
"We need to wait a little and draw some conclusions after the Tenerife game."
Villarreal visit bottom club Xerez in their next outing, and then have home advantage for consecutive matches against 18th-placed Malaga and promoted Tenerife.
"It's an unfamiliar situation for us and difficult to understand, but we can't let heads drop because we have the quality to get out of this," he added.
"It's at times like these when doubts arise, and you lose quality and confidence, so I hope it doesn't continue much longer for the good of the club."
Villarreal were booed off the pitch at the Madrigal on Sunday after being held to a 0-0 draw by Espanyol, who had played 75 minutes with 10 men.
The east-coast club finished fifth last season before Manuel Pellegrini ended his five-year spell as coach to take the helm at Real Madrid.
His replacement Ernesto Valverde was given the backing of club president Fernando Roig after Sunday's game.
"The president came down (to the dressing room) to call for calm and this is very important for the team because it helps... to know everyone is with us," Spain international Santi Cazorla said.