Rob Howley was left concerned over the fitness of Jamie Roberts and Alun Wyn Jones after both players were forced off against Argentina.
The absence of both players proved costly as Wales slipped to a 12-26 defeat in Cardiff, their fourth consecutive loss in Test matches.
"Jamie has mild concussion - to say the least - and Alun Wyn has done his AC [joint capsule in collarbone] and right now it does not look good. It is certainly going to test the strength in depth of our squad," said Howley.
As for the result itself, Wales struggled to put together a cohesive attack and also missed 19 tackles in defence, allowing Argentina plenty of scoring opportunities.
"I'm disappointed, frustrated and annoyed. But we will dust ourselves off and look forward to the Samoan challenge on Friday," added Howley.
"There is no doubt that Argentina have gained the experience of their exposure in the Rugby Championship against New Zealand, South Africa and Australia and that showed in the way they played the game.
"We looked to be in second gear and the last 30 minutes were hugely disappointing.
"We trained particularly well leading up to the game but the Rugby Championship has taken this Argentine side to another level in tempo, pace and intensity and we very much came second.
"Obviously this is a set-back but we have three more games to go and plenty to play for - it is important we go into those matches with self belief and confidence.
"History suggests that Wales get stronger as the autumn series goes on and I am sure that will happen. We've got three games to go, a hugely physical challenge with Samoa next week so it's important we get back on the training paddock and sort things out.
"International rugby is about scoring tries. It hasn't been a problem for us in the recent past but today as I say, we struggled with possession and territory.
"That was an area of concern in terms of struggling with territory and possession and not being able to put Argentina under the pressure we wanted them to, particularly in their 22 metre area.
"We have to work hard and be smart and there were areas today where we weren't smart. We have to improve all round."