The Manchester City striker surprisingly started on the bench in the 1-1 draw with World Cup holders Italy in Cape Town, only coming on as a late substitute.
The injury-plagued forward revealed a minor problem had convinced coach Gerardo Martino to leave him among the replacements but believes he is ready to hit the ground running now.
Asked about his absence from the starting line-up, Santa Cruz said: "It's very hard to pick players from our team, we are players playing in hard leagues and anybody can play.
"After the last friendly I finished with some discomfort in my leg and then, of course, as we have such good players there is no need to risk anything.
"I was not really 100%. I had a muscle problem and didn't know if I could play from the beginning, so I think the coach took the best solution and the right choice.
"It's been the story with injuries through all my career, not just this season!"
He added: "It's disappointing but something I've lived with through my career.
"Right now I think we have an advantage that we have such players in the team and there's no need to force people in. In the last World Cup I risked a lot to play and there's no point now.
"I hope I'll be fully fit for the Slovakia match, I felt okay against Italy when I came on felt I could have played longer.
"We've got six days between games and that should be enough to be ready."
Santa Cruz is justifiably upbeat about his side's Group F prospects in South Africa.
"We obviously want to make it into the next phase from the first stage," he said.
"We want to go at least to the quarter-finals because in Paraguayan history it's never been done. But you never know."