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Cold pathogen refers to the severe, killing cold air of winter. However, there are differences in "mào" (encountering), "shāng" (injuring), and "zhōng" (striking). "Mào" refers to the skin receiving cold, manifesting as coldness in the nose, distension in the eyes, alternating chills and fever, and a slight feeling of stiffness and fatigue. "Shāng" refers to the syndrome of transmission between meridians described below. "Zhōng" occurs due to weak constitution and loose interstices (pores/skin texture), allowing cold pathogen to directly enter the Three Yin meridians without transmitting from the exterior; its symptoms include cold limbs, colicky pain in the umbilical and abdominal regions, and a deep, slow, and forceless pulse. Generally, from after Frost's Descent until before Spring Equinox, the heavenly mandate is severely cold, with water freezing and ground hardening, forming killing qi. If humans encounter this and fall ill immediately, it is named "Zhèng Shānghán" (True Cold Damage). If it does not cause immediate illness but cold toxin hides in the skin and muscles, erupting in spring, it is called "Wēnbìng" (Warm Disease). If it erupts in summer, it is called "Rèbìng" (Heat Disease). The ancients collectively referred to these as Shānghán.

However, Shānghán enters from the exterior to the interior and must transmit sequentially. For instance, if occurring within one or two days, accompanied by headache and stiff neck, back and spine stiffness, fever, aversion to cold, and floating pulses at all three positions (cun, guan, chi), it is a disease of the Taiyang Meridian (Greater Yang Meridian). If transmitted sequentially, it will inevitably transmit to the Stomach (Yangming Meridian). If occurring within two or three days, accompanied by eye pain, dry nose, insomnia, tidal fever in the afternoon, aversion to heat rather than cold, and long pulses at all three positions, it is a disease of the Yangming Meridian (Yang Brightness Meridian). If transmitted sequentially, it will inevitably transmit to the Gallbladder (Shaoyang Meridian). If occurring within three or four days, accompanied by chest and hypochondriac pain, deafness, alternating chills and fever, vomiting, and bitter taste in the mouth, with wiry pulses at all three positions, it is a disease of the Shaoyang Meridian (Lesser Yang Meridian). If transmitted sequentially, it will inevitably transmit to the Spleen (Taiyin Meridian). If occurring within four or five days, accompanied by abdominal fullness, dry throat, spontaneous diarrhea without thirst, and deep, fine pulses at all three positions, it is a disease of the Taiyin Meridian (Greater Yin Meridian). If transmitted sequentially, it will inevitably transmit to the Kidney (Shaoyin Meridian). If occurring within five or six days, accompanied by dry mouth and tongue with thirst, and deep pulses at all three positions, it is a disease of the Shaoyin Meridian (Lesser Yin Meridian). If transmitted sequentially, it will inevitably transmit to the Liver (Jueyin Meridian). If occurring within six or seven days, accompanied by irritability, thirst, and contraction of the scrotum, with slightly relaxed pulses at all three positions, it is a disease of the Jueyin Meridian (Terminal Yin Meridian). Thus, the manifestations and symptoms of the Six Meridians are clarified.

However, even though the Six Meridians are clarified, they should not be viewed as a fixed and unchangeable sequence. Some begin in the Taiyang meridian and transmit sequentially into the Yin meridians, ending in Jueyin. Some do not transmit from Taiyang to Yangming or Shaoyang, but instead transmit to Shaoyin. Some do not enter through the Yang meridians but directly invade the Yin meridians. Some remain in one meridian throughout without transmitting. Some involve simultaneous affliction of two or three Yang meridians, known as Hébing (Combined Disease). Some involve sequential affliction of Taiyang and Yangming, known as Bìngbìng (Concurrent Disease). Due to the lack of explicit text in the classics regarding these complexities, later practitioners have treated them recklessly, causing much harm.