The Lions, without some of their key players, face fellow title chasers Western Province at Newlands on Saturday.
The visitors are without flyhalf Elton Jantjies, winger Jaco Taute and prop CJ van der Linde, who were all called up to the Bok squad this week.
"We know how important this game is," Lions coach Johann Ackerman said ahead of the clash.
"We have a lot of players that are currently playing at the Springboks, but that just gives another young, talented player the opportunity to come through the ranks,"
Ackerman said they would turn to veteran Butch James, who replaces Jantjies at flyhalf, for inspiration.
"Butch has played many games at flyhalf and we trust his decision making," he said.
"He will be one of our go-to guys on the day."
Province coach Allister Coetzee said the hosts were expecting a strong challenge against the title holders.
"Yes, the Lions have guys like Elton Jantjies and Jaco Taute who are at the Springboks and thus not available for the game, but that doesn't make them a weaker side," Coetzee said.
"Now they have Butch James at flyhalf, and he poses another threat."
Province are fresh off a crushing victory over Griquas, having earned a lot of good first-phase possession, and Coetzee said they would look for more of the same against the visitors.
"We did well in our line-outs and scrums last week and will again look to those platforms to give us some good go ahead ball. It is essential that we secure those phases," Coetzee said.
Province are without playmaker and fullback Gio Aplon, who is out with an ankle injury, as well as flyhalf Gary van Aswegen, who also hurt his ankle and will be off the field for the rest of the season.
Scrumhalf Louis Schreuder picked up a knee injury, but Province were hoping he would recover before they kicked off against the Lions.
While the battle for the top position was set to continue, the struggle to keep clear of the relegation zone was the main focus point for the Free State Cheetahs and Griquas who were geared up to meet in Bloemfontein.
"This is one of the most important games of our season," said Griquas coach Pote Human.
"A couple of weeks ago we were doing pretty well, but then we lost against Western Province.
"Now our game against the Cheetahs carries so much more importance, because we need points to go to the semi-finals."
Although the Cheetahs, struggling with injuries to many of their seasoned players and without Springboks Adriaan Strauss and Coenie Oosthuizen, were at the bottom of the log, Human remained cautious and refused to underestimate the prowess of the Bloemfontein-based side.
"They can beat any team on any day, and for that reason you can never go to Bloemfontein unprepared," Human said.
"They had a bad run of form lately, but they remain a quality side."