At first blush — and the Patriots certainly were left red-faced last Sunday in Foxboro — there seems to be a bit of an overreaction to the franchise’s first regular-season loss since Dec. 10, 2006, which came against (how weird is this?) the Dolphins in Miami.

The score of that game was 21-0, and at the time it was almost as shocking as last Sunday’s 38-13 embarrassment at Gillette Stadium, also at the hands of the Dolphins, who came to New England having lost 20 of their previous 21 games.

The powerful Patriots, on the other hand, had won an NFL-record 21 in a row and were coming off their fourth Super Bowl appearance — albeit their first Super Bowl loss — in seven seasons.

But it is, after all, the NFL, where the mantra heard since the days of leather helmets and no face masks — or at least since the days of the league’s late Commissioner and Publicist Supreme, Pete Rozelle — has been “on any given Sunday.”

So it’s very likely that beyond the borders of the six-state region that the Patriots call home, fans are asking: What’s the big deal?

The Patriots had to lose sometime. The fact that it was the Dolphins who beat them is disconcerting, but, before last year’s sweep of Miami in a season in which the Fish were swimming upstream while going 1-15, Miami had beaten New England in three of their previous five meetings.

Why then, NFL fans from afar may well wonder, is their such hand wringing in New England over one lousy loss, as ugly as it may have been?

Yes, after winning five straight division titles, the Pats suddenly find themselves behind the 3-0 Bills in the AFC East. But they’ve beaten Buffalo nine straight, and 14 of the last 15, so are they really all that worried about catching the Bills?

Yeah, they are.

Because there’s a huge difference between the quarterback who ran the offense in the first 20 games of that record-setting winning streak and the guy who was at the helm for the last one — and for the first regular-season defeat in more than a year, as well.

If two-time Super Bowl MVP Tom Brady had been at QB last Sunday — OK, OK, if Brady had been at QB last Sunday, the Patriots would have beaten the Dolphins, 38-13, instead of the other way around, but we’re speaking hypothetically here — then the strange setback could have been dismissed as an aberration.

Surely, the thinking would have been, the Pats will bounce back against the 49ers, who are quarterbacked by a guy that was cut from the New England practice squad after a month in the fall of ’06 and then was on the roster of three other teams before signing with San Francisco last February.

Now, however, Patriots fans don’t know what to think.

The three teams the Pats have played so far were a combined 9-39 last season. They’re off to a combined 2-7 start this season.

In the opener at Foxboro, New England needed a last-minute, goal-line stand to hold off Kansas City — which may be as close to winning a game as the struggling Chiefs come all year.

The Jets, despite an array of acquisitions in the offseason, highlighted by Hall of Fame QB Brett Favre, so far appear to be dangerous only to themselves.

And Miami — last Sunday’s upset win not withstanding — is highly unlikely to be a playoff threat in 2008.

The 2-1 Pats will have had two weeks to get ready to play the 49ers, who, according to a recent headline in the San Francisco Chronicle, are “brimming with confidence after beating (the Detroit) Lions.”

Brimming with confidence after beating the Lions?

That’s like brimming with confidence that you’ll write a Pulitzer Prize-winning novel because you correctly recited the ABCs. It’s tantamount to brimming with confidence that you can cook a seven-course, gourmet meal because you just made a peanut-butter-and-jelly sandwich.

Even the Chiefs might be able to beat the Lions, who finally fired their obviously overmatched general manager, Matt Millen — the former Raiders linebacker who compiled a record of 31-84 in 7-plus seasons in Detroit.

The 49ers play today in New Orleans, so reality may hit them hard in the Big Easy, but the fact is that while they surely respect the Patriots, they’re probably not quivering in their cleats over the prospect of playing the defending AFC champions.

Especially with Cassel at quarterback.

The last time he started a game in California was in the high-school playoffs in 1999. In five seasons at Southern Cal, he never once got the starting nod.

But with Brady out for the season, Cassel has started the last two games for the Patriots — “managing” the game, as Bill Belichick likes to say, nicely in his NFL debut against the Jets, but then managing to put just 13 points on the board against a Miami defense that had been riddled for 34 by the Cardinals the previous week in Arizona.

Combine that with the fact that the New England defense was utterly befuddled by Miami’s version of the ancient, single-wing offense, and it’s understandable why Patriots fans are more than a little concerned that after having won 21 in a row, the Pats very well could lose two back to back. Or three, considering that they go from San Francisco to San Diego. Or four, since they then take on the currently undefeated Broncos in a Monday-night game in Foxboro. Or — well, you get the point.

jdonalds@projo.com