Wits were booted out of the second-tier continental tournament by Egyptian side Smouha last week, following a 1-0 aggregate defeat.
South Africa are now left with three teams competing in continental club football, including SuperSport United, Platinum Stars – both in the Confed Cup group stage – and Mamelodi Sundowns, who return to the CAF Champions League group stage.
Mosimane, who lead The Brazilians to their maiden Champions League title last year, has repeatedly urged PSL teams to start taking CAF competitions seriously.
"I am disappointed that we couldn't have four teams [in CAF]. There are no excuses, we should have four teams," said Mosimane.
"Dr. [Irvin] Khoza said he foresees a future, or wishes to see two South African teams in the semi-finals of the Champions League.
"There is no reason SuperSport United and Platinum Stars could not be in the semi-finals of the Confederation Cup, there is no reason.
"Look how SuperSport brushed aside the Liberians, it's possible, it's a mindset, if you want it you can [achieve it]."
The Clever Boys were restricted to a goalless stalemate in their first leg tie at home a fortnight ago, before going down 1-0 in Alexandria last weekend.
"I saw Smouha playing in Egypt, I think Wits could have beaten Smouha," he added. "I don't know, maybe next year.
"It's not about quality but about mindset, you need to fight a little bit and you will get there
"I foresee SuperSport and Dikwena going through [to the knockout phase]. You just have to get second position [in the group] and already you are in the last eight."
Mosimane believes that the new Total sponsorship of CAF provides worthy incentives of playing in Africa, which is enough to motivate South African teams to play in the continental tournaments.
United and Stars are set to pocket R3,4-million just for qualifying for the Confederation Cup group stage, and will add to the sum upon progressing further.
"By the way, there is a lot of money now. Just for SuperSport to qualify, [they get] 40 percent of the league [prize money]," he said.
"It's one match for us to go to the group stages, it's one match. I think the spin offs are big, why do you want to fight 30 games and win R10 million?
"Just go to Japan [FIFA Club World Cup] and you will see how much you get, it's more than the league just [to play] one match."
'Jingles' concedes that the struggles faced with travelling and accomodation in Africa may not always be comfortable, but argues that the prestige and reward of fighting through it is always worth it.
"Football has changed. As South Africa, we need to look at it properly. We are saying we don't want to go there, we complain about the hotel, what about the hotel?
"You complain about the pitch and want to play in Champions League, then you complain about transit but you sitting at the airport, then don't go!
"You wanna go to Cape Town here – two-hour flight, the airport is nice, you land and the bus is there [waiting] – no, we wait there in the sun and then you will play in the [Club] World Cup," he concluded.