City fielded left-back Javi Garrido and Brazilian midfielder Elano Blumer, just two days after they signed for the Blues, while Kasper Schmeichel was given a surprise call-up following injuries to Andreas Isaksson and Joe Hart in midweek.
City fans gave a rousing welcome to both new owner Thaksin Shinawatra and Ricky Hatton but the Spaniards proved to be party poopers, taking the lead in the 10th minute.
New midfielder Gelson Fernandes gave the ball away in the City half and although Schmeichel saved Joaquin's effort, David Silva was on hand to turn in the rebound.
City responded well with Elano impressing, the Brazilian international winning possession before Michael Johnson curled a shot against the crossbar. Elano then had a shot saved and crossed for Rolando Bianchi to head against the bar.
Bianchi and Martin Petrov showed some nice touches in the second half while Schmeichel did well as he twice came out of his area to clear.
Geovanni, a half-time replacement for Elano, almost claimed a spectacular late equaliser with a scissor kick that went inches over the bar.
But City had to settle for a defeat from their final friendly, wrapping up a pre-season programme of 4 wins and 2 defeats.