Extrusion adjustment
SHORT ANSWER

You're not supposed to do the single-wall perimeter thickness test to calibrate Simplify3D. That screws up the extrusion volume. The correct volume calibration procedure for S3D is: 


Measure actual average filament diameter and input that
Print a 100% infill calibration cubes
If the print is over-extruded (top or sides bulging), decrease Extrusion Multiplier by about 0.05 and try again. If the print is under-extruded or looks clean, increase Extrusion Multiplier by about 0.05 and try again.
Repeat as needed to dial it in. The correct value of Extrusion Multiplier is the largest value that does not produce over-extruded prints. This produces minimum void volume and strong parts.
In the future, that specific material+extruder combination will always have the same extrusion multiplier. You only need to measure and input filament diameter and you will always get accurate volume output. (And if you use high-quality filament with consistent diameter, you don't even really need to measure the diameter.)


If you really want to measure perimeters, you can do 3 perimeters and divide the measurement by 3. That takes into account most of the overlap and will be much closer to accurate than a single-perimeter measurement.

COMPLETE ANSWER

The goal here is to fill the print volume as completely as possible (at least in the "solid" parts of the print like perimeters, roofs, and floors). Empty space between strands doesn't contribute to part strength. In fact, voids act as failure initiation sites by concentrating stresses. Because extruded strands come out with rounded edges, they have to be overlapped to squeeze plastic into gaps and minimize "corner voids." That looks like this:



Where the bulges overlap, the excess plastic gets pushed into the corners to mostly fill the voids. It's very difficult to get 100% packing density, but you can get pretty close if you calibrate volume correctly.



You DO NOT want to space the strands without overlap. That makes very weak prints and looks like this:



To get the right amount of strand overlap, the slicer has to do some math and make some assumptions about how you're calibrating it. This is not uniform between software packages. So it's important to understand what "extrusion width" means to different slicers. For a couple prominent examples:


Slic3r treats "extrusion width" as the measured outside dimension of a stack of strands. Adjacent strands are then positioned closer together than the nominal width according to a somewhat complicated equation to get sufficient overlap for bonding.
S3D treats "extrusion width" as the average width of the stack of strands, which is the equivalent width if the plastic strands were extruded as ideal rectangles instead of a stack of ovals. Adjacent strands are positioned 1x nominal extrusion width apart. That provides the correct amount of overlap without any extra math. But each individual strand is really somewhat wider than the nominal "width."




Both of these techniques can produce the exact same output if calibrated properly, but they require different calibration techniques because they calculate the plastic volume and adjacent strand spacing different ways. 

It's important to understand that S3D spaces its strands 1x extrusion width apart. When you use the measured perimeter thickness to calibrate Simplify3D for extrusion width setting = measured thickness, you get under-extruded prints with no strand overlap. S3D's strands must measure wider than the "width" setting to get the correct overlap. 

In practice, S3D's code is smart enough to know how this affects print dimenions, and will adjust perimeter positions to get accurate overall dimensions. But single-wall test boxes will be thicker than expected. 

The downside to the way Slic3r calculates volume is that it is only accurate for strands that are shaped like ovals. And that is only an accurate assumption when [extrusion width > nozzle width + layer height]. The strand must be wide enough for molten plastic to flow sideways and develop the circular bulge cross-section. So people almost always print with wider strands in Slic3r than is strictly necessary. The volume calculations don't work all that well with thin strands. Whereas S3D's volume calculation method works fine with pretty much any extrusion width greater than layer height and greater than nozzle diameter. 

There are pros and cons to both systems. You just need to understand the correct calibration technique for each.