The Blues travelled to South Africa depleted by injuries and international call-ups but on the back of three consecutive wins in the competition.
However, they were made to pay for a sluggish start as the Cheetahs came flying out of the blocks.
The hosts raced into a 14-0 lead thanks to early tries from Shaun Venter and Sibhale Maxwane and the damage was done.
Steve Shingler opened his side’s account with a penalty but on the stroke of half-time they were dealt a knockout blow as the ball was snatched and Maxwane went the length.
Manoa crashed over mid-way through the second-half but it was too little, too late as Cardiff Blues left South Africa empty-handed ahead of next week’s visit of Zebre.
The Blues had come out of the blocks slowly in their last three encounters and it was a case of Déjà vu in Bloemfontein.
Playing at altitude and in sweltering heat, it was never going to be easy against a full-strength Cheetahs outfit at the Toyota Stadium, and they found themselves 14-0 down after just 12 minutes.
The South African outfit first struck on eight minutes when their captain Shaun Venter took advantage of a gap at the breakdown to snipe through and race 40 minutes later.
Tian Schoeman added the extras and four minutes later, the Cheetahs struck for a second try against the run of play.
It was Cardiff Blues on the attack when Lloyd Williams was intercepted but the ball was lost in contact and Joseph Dweba was able to release Sibhale Maxwane.
The electric wing kicked ahead and displayed his devastating pace to collect the ball in the corner. Schoeman was again on target as he booted the hosts into a 14-0 lead.
Wales’ Captial Region worked their way into the encounter, with play swinging back-and-fore and both teams attacking at any opportunity.
Steve Shingler slotted the Blues first points on 20 minutes when the pack won a scrum penalty.
Another penalty, tapped quickly by Williams, almost led to the Blues opening try as Matthew Morgan went on the counter-attack. He went between two defenders before releasing Harries on the outside.
But the Wales Sevens star did not have the legs to outstrip the Cheetahs and he was forced inside, where he found Olly Robinson in support. He was tackled short and two phases later possession was lost.
The Blues continued to threaten but to no avail and they were dealt a devastating blow just before half-time. Having kicked a penalty to the corner, they were edging towards the whitewash but somehow the ball fell into the hands of Venter and he fed Maxwane.
He still had plenty to do but he simply had too much gas as he raced away for his second of the night. Schoeman converted to give his side a 21-3 lead at the break.
That could have been extended early in the second half as the Cheetahs continued to threaten on the counter-attack. It was from a kick return that they looked to have claimed a fourth
Malcolm Jaer embarked on the counter and kicked ahead but replays showed the chaser was offside as the Blues were let off the hook.
As the clock passed the 50 minute mark, the Blues began making changes and introduced the likes of Nick Williams and Samu Manoa, as well as a whole new front-row.
The ball-carrying prowess and size of Williams and Manoa, instantly had an impact both in the loose and at scrum time.
And on 65 minutes, Manoa, making his Guinness PRO14 debut, charged down Schoeman and collected to give his side a glimmer of hope.
However, despite having a number of opportunities in the final quarter to give themselves a shot of winning or to secure a losing bonus-point, crucial errors continued to be made. The Blues return to Cardiff tomorrow and face Zebre at Cardiff Arms Park a week Sunday.