Matsuzaka allowed five runs on seven hits in 5 1/3 innings. He walked one, struck out five, hit two batters and threw 54 of 90 pitches for strikes.
Boston placed Matsuzaka on the disabled list last May 17 and he underwent Tommy John surgery on June 10.
In four rehab starts, he's pitched 18 2/3 innings and allowed nine earned runs on 18 hits, with six walks and 19 strikeouts. Matsuzaka's ERA elevated to 4.34 from 2.70 after Saturday's game.
"I was pretty satisfied with my fastball ... it improved from my last outing," said Matsuzaka, who topped out at 93 and consistently threw that pitch in the 88-to-92 mph range. "Areas that I'm not too happy about were my offspeed pitches."
PawSox manager Arnie Beyeler agreed with the right-hander.
"Comparing it to the other night [May 7], I didn't see stuff as crisp," Beyeler said after a 7-6 victory for Pawtucket. "I saw more thigh-high-to-belt-high than thigh-high-to-knee-high [pitches].
"I think that sums it up. He was flat and not crisp tonight. He was around the zone and threw some strikes. But he had a little trouble finishing off hitters. I think that was because his command was off. He had better plane the other night. He was down more."
Of even more importance is the decision Boston must make regarding Matsuzaka, whose 30-day rehab window closes May 23. At the most, that allows for one more rehab start.
"My elbow felt better than it did last time and my body felt great," Matsuzaka said. "But looking at tonight's results, there are obvious areas I need to work on. That would be command of my offspeed pitches. Most of the hits came off my offspeed pitches."
Matsuzaka encountered a jam in the third when Gregorio Petit and Ezequiel Carrera sandwiched singles around a strikeout of Ben Copeland. Andy LaRoche's hit-and-run single scored Petit. But Matsuzaka averted further damage by retiring Cord Phelps on a foul pop and Chad Huffman on a liner to right.
Matsuzaka's most impressive inning was the fourth, when he fanned the side in order. He caught Beau Mills, Russ Canzler and Matt Pagnozi looking at third strikes.
But Matsuzaka hit Petit leading off the fifth and Copeland pulled a two-run homer to right field.
The sixth commenced in a similar manner, as Matsuzaka hit Huffman to lead off the frame and then allowed a two-run homer to Canzler, which gave Columbus the lead.
Copeland's homer came on a changeup, while Canzler's came on a cutter.
"My command on those pitches wasn't there," Matsuzaka said. "But when I threw more fastballs, the results showed. They were good. When I threw more offspeed pitches, the results didn't come through."
The plan going into the game was for Matsuzaka to throw between 90 and 95 pitches or six innings.
"He pitched into the sixth inning," Beyeler said. "It wasn't like it was bad stuff. He battled. He got guys out. But looking at total stuff and things like that, I thought the stuff was a little bit crisper the last time out and was located a little better.
"My take is, you get the ball down. If you're a pitcher and you're working up in the zone, you get the ball down."