It looked like Juande's tactical switch around at the interval had done the trick again when Robbie Keane's double - a penalty after Dimitar Berbatov was brought down, a volley from Tom Huddlestone's fine pass - cancelled out Birmingham's 1-0 half-time lead.
Berbatov then hit the post at 2-1 but everything changed between 60 and 70 minutes.
First, Cameron Jerome drilled a low shot into the corner to equalise, then Robbie Keane was shown a somewhat harsh straight red card after a tackle on Fabrice Muamba and then Gareth Bale hobbled out of the action after falling awkwardly in a challenge.
At that point, a draw would have still been a frustrating result but then Sebastion Larsson added insult in injury time by smashing home a 30-yard winner for the visitors.
"I don't think it's a fair result after the huge effort we put into getting back into the game," said Juande afterwards. "We had a chance with Berbatov to make it 3-1 and to let in a goal like that when the time was up was a blow because we were much, much the better side.
"It's difficult but these things happen in football. You can win, lose or draw and we've lost. We attacked well, we had many chances, much more than Birmingham, but we've lost.
"We played well and hoped to win the game, especially after we managed to turn the scoreline around, but we've come away with nothing."
Naturally, Juande was asked his opinion on key decisions - the penalty awarded against Younes Kaboul for his tackle on Garry McSheffrey in the first half and the Keane straight red card.
"These are decisions referees have to make," he said. "You can see on television that it wasn't a penalty and the sending off was harsh. Usually with this type of action the referee would show a yellow card and it certainly wasn't deserving of a red card.
"It's important to emphasise that we lost this game though, not the referee."
Juande Ramos insisted we were much the better side and unlucky to fall to the first defeat of his reign as Head Coach against Birmingham on Sunday.