On 6 October 2009, Negredo received his first call to the Spain senior team, for a 2010 FIFA World Cup qualifier against Armenia on the 10th, following the injuries of David Villa and Daniel Güiza.
Pada 6 Oktober 2009 Negredo menerima panggilan pertamanya ke tim senior Spanyol, untuk kualifikasi Piala Dunia FIFA 2010 melawan Armenia (pada tanggal 10), menyusul cedera David Villa dan Daniel Guiza.