Mark me - Margin, "look unto." Literally, "Look upon me. That is, attentively look on me, on my sufferings, on my disease, and my losses. See if I am a proper object of repreach and mockery - see if I have not abundant reason to be in deep distress when God has afflicted me in a manner so unusual and mysterious.
And be astonished - Silent astonishment should be evinced instead of censure. You should wonder that a man whose life has been a life of piety, should exhibit the spectacle which you now behold, while so many proud contemners of God are permitted to live in affluence and ease.
And lay your hand upon your mouth - As a token of silence and wonder. So Plutarch, de Iside et Osiride, "Wherefore, he had laid his finger on his mouth as a symbol of silence and admiration - ἐχεμυθίας καὶ σιωπῆς σύμβολον echemuthias kai siōpēs sumbolon."

Mark me, and be astonished - Consider and compare the state in which I was once, with that in which I am now; and be astonished at the judgments and dispensations of God. You will then be confounded; you will put your hands upon your mouths, and keep silent. Putting the hand on the mouth, or the finger on the lips, was the token of silence. The Egyptian god Harpocrates, who was the god of silence, is represented with his finger compressing his upper lip.

Mark me, and be astonished, and lay [your] hand upon [your] (c) mouth.
(c) He charges them as though they were not able to comprehend his feeling of God's judgment, and exhorts them therefore to silence.

Mark me,.... Or "look at me" (n); not at his person, which was no lovely sight to behold, being covered with boils from head to foot, his flesh clothed with worms and clods of dust, his skin broken, yea, scarce any left; however, he was become a mere skeleton, reduced to skin and bone; but at his sorrows, and sufferings, and consider and contemplate them in their minds, and see if there was any sorrow like his, or anyone that suffered as he did, and in such pitiful circumstances; or that they would have a regard to his words, and well weigh what he had said, or was about to say, concerning his own case, or concerning the providences of God with respect to good and bad men, and especially the latter:
and be astonished; at what had befallen him, at his afflictions, being an innocent man, and not chargeable with any crime for which it could be thought that these came upon him; and at the different methods of Providence towards good men and bad men, the one being afflicted, and the other in prosperous circumstances, see Job 17:8;
and lay your hand upon your mouth; and be silent, since such dispensations of Providence are unsearchable, and past finding out; and, as they are not to be accounted for, are not to be spoken against: and it would have been well if Job had taken the same advice himself, and had been still, and owned and acknowledged the sovereignty of God, and not opened his mouth in the manner he had done, and cursed the of his birth, and complained of hard treatment at the hand of God perhaps his sense may be, that he would have his friends be silent, and forbear drawing the characters of men from the outward dealings of God with them. This phrase is used of silence in Job 29:9; thus Harpocrates, the god of silence with the Heathens, is always pictured with his hand to his mouth.
(n) "respicite ad me", Pagninus, Montanus, Junius & Tremellius, Piscator, &c.

lay . . . hand upon . . . mouth-- (Proverbs 30:32; Judges 18:19). So the heathen god of silence was pictured with his hand on his mouth. There was enough in Job's case to awe them into silence (Job 17:8).

Mark - Consider what I am about to say concerning the prosperity of the worst of men, and the pressures of some good men, and it is able to fill you with astonishment. Lay, &c. - Be silent.