La Liga returned this past weekend with Barca comfortably dispatching Mallorca, Messi contributed two assists and a goal of his own in a 4-0 win, meaning he needs just two more to reach 700 for Barcelona and Argentina.
Though Setien is in awe at Messi's numbers, he has also praised his contributions in other areas while also confirming that he is fully fit after picking up a knock in training last week.
Setien said: "Leo is fine. You don't only have to assess the goals he scored, but also the rest of his contributions, like assisting. That gives us a lot of points.
"It's an astronomical number. I think he's reached 700 goals and that's why he's the best player in the world."
Barcelona return to action on Tuesday against Leganes, and there could be some rotation from the league leaders, with Luis Suarez in contention for a start after returning from injury off the bench on Saturday.
"I have not decided if Luis Suarez will start tomorrow, I have to talk to him. We have to be very cautious, after long injuries muscle problems can start to appear. We must take care," he admitted.
"Luis Suarez could be one of the players to rest tomorrow or at a later time. Luckily, we have more players. We have a team to adapt to the circumstances.
"[Antoine] Griezmann is indisputable, he is a great footballer, we continue to count on him, he will continue to play a leading role because he is important for the team and the club, but there are also other players that we have to use."
After 28 matches played so far in the Spanish top flight, the Catalan side currently sit top on 61 points, two ahead of rivals Real Madrid.