Portmon is a utility that monitors and displays all serial and parallel port activity on a system. It has advanced filtering and search capabilities that make it a powerful tool for exploring the way Windows works, seeing how applications use ports, or tracking down problems in system or application configurations. link

The Null-modem emulator (com0com) is a kernel-mode virtual serial port driver for Windows. You can create an unlimited number of virtual COM port pairs and use any pair to connect one COM port based application to another. link

• Java communications API
• RXTX

PySerial is a 100% Python package. On windows it relies on the Python Win32 Extensions with the Searial class being a wrapper of a win32file

• PySerial

The Twisted libraries implemented a selectable serial port on windows: win32serialport.py

Note: The write/read API is expecting characters

import serial
 
s = serial.Serial('\\\\.\\CNCA0')
 
print "Writing..."
for i in range(0x00, 0xFF, 5):
    data = [i , (i+1), (i+2), (i+3), (i+4)]
    message = ''.join([chr(d) for d in data])
    s.write(message)

import serial
 
s = serial.Serial('\\\\.\\CNCB0')
 
print "Reading..."
for i in range(0x00, 0xFF, 5):
    message = s.read(size=5)
    data = [ord(c) for c in message]
 
    print ' '.join(['0x%02x'%d for d in data])