The Colombian was not in Van Gaal's matchday squad for the 1-0 Premier League loss at Old Trafford as Van Gaal's strikeforce failed to muster a shot on target.
United were downed by a second-half Dusan Tadic strike with Southampton moving third in the Premier League as a result of the win but Van Gaal stuck by his squad selection post-match.
When pressed on the decision, the Dutchman explained it was merely a case of ensuring the composition of his bench was appropriate, given fitness concerns over the likes of Luke Shaw, Angel Di Maria and Daley Blind.
Asked by reporters whether he regretted the decision, he explained: "No. The reason is that I have to see and compare players in my selection, that is what I'm doing when we train.
"Then I have to look at the composition of my selection and what I can do during the match. What players I have and I want to play with those kind of players, did not have match rhythm.
"So I had to change for example, Shaw and Di Maria, I know that in advance. Normally, I would have changed Di Maria for [James] Wilson because I also need speed in attack.
"I know in advance I have to change Luke Shaw and normally I have to change Daley Blind because he also needs match rhythm.
"In advance I know I have to change defensive players, when you see the composition of the bench and I want to change the playing style, which I did with [Marouane] Fellaini, then I don't have any position for a second striker.
"This is this moment, next week is another moment. Shall I decide another way?"
Van Gaal also confirmed striker Robin van Persie has suffered an ankle problem and will have a scan on the injury on Monday.
